Fluid cartridge and apparatus for processing a fluid cartridge
Patent Information
- Application Number
- CN202580023946.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2024-04-30
- Filing Date
- 2025-04-29
- Publication Date
- 2026-10-30
AI Technical Summary
然而,具有与反应室的仅一个壁接触的热装置可以导致反应室内室的与热装置接触的壁与不与热装置接触的相对壁(即,与光学装置接触的壁)之间的温度梯度
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Figure CN123022500A_ABST
Abstract
Description
Cross-references to related applications
[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 640,761, filed on April 30, 2024. Technical Field
[0002] This disclosure relates to systems and methods for performing sample preparation and sample analysis operations within a fluidic chamber, the methods comprising: realizing fluid movement through channels between chambers within the chamber, sample purification, sample / reagent mixing to form a sample reaction mixture; heating and / or cooling the sample reaction mixture; and detecting a signal indicating a test result from the sample reaction mixture. Background Technology
[0003] Determination procedures performed in test platforms, such as fluid chambers, require precise movement of fluid throughout the chamber. This precision necessitates accurate device control and robust process control in both the volume and time of fluid movement.
[0004] In addition, assay procedures often require the application of thermal energy (isothermal energy or thermal cycling energy) to the reaction chamber to induce a desired reaction within the reaction mixture contained within the chamber. Such assay procedures may also involve detecting optical emission signals emitted from the contents of the reaction chamber during a thermally induced reaction and / or applying excitation optical signals to the contents of the reaction chamber.
[0005] Applying heat energy to the reaction chamber requires placing a thermal device, or heater (e.g., a thermoelectric module), in thermal contact with the outer surface of the reaction chamber wall. This typically requires physical or proximity contact between the thermal device and the outer surface of the wall. Similarly, detecting optical emission signals from the contents of the reaction chamber and applying optical excitation signals to the reaction chamber requires placing an optical detector or optical emitter (light source) in physical or proximity contact with the outer surface of the reaction chamber wall, or placing an optical emitter (e.g., a waveguide, such as a light pipe or optical fiber) extending from the detector and / or emitter in physical or proximity contact with the outer surface of the reaction chamber, so that the optical signal can be transmitted from the emitter to the reaction chamber and / or so that the optical signal can be transmitted from the reaction chamber to the detector.
[0006] A thermal device positioned in contact with the outer surface of the reaction chamber can interfere with an optical device (e.g., a detector / emitter / transmitter) positioned in contact with the same outer surface of the reaction chamber, if the placement of the optical device in contact with the same outer surface of the reaction chamber is not prevented, and vice versa. Therefore, thermal devices are typically positioned in contact with the outer surface of one wall of the reaction chamber, and optical devices are positioned in contact with the outer surface of another wall (typically the opposite wall) of the reaction chamber. However, having a thermal device in contact with only one wall of the reaction chamber can result in a temperature gradient between the wall of the reaction chamber in contact with the thermal device and the opposite wall (i.e., the wall in contact with the optical device). This thermal gradient can lead to inaccurate and / or inconsistent test results. Of course, placing the thermal device on both opposite walls of the reaction chamber to minimize or eliminate this temperature gradient may interfere with the detector's ability to detect optical emission signals from the contents of the reaction chamber and / or the transmitter's ability to apply optical excitation signals to the contents of the reaction chamber. Summary of the Invention
[0007] The following is a simplified overview to provide a basic understanding of some of the aspects described herein. This overview is not a comprehensive review of the claimed subject matter. It is intended neither to identify the key or essential elements of the claimed subject matter nor to depict its scope. Its sole purpose is to present some concepts in a simplified form as a prelude to the more detailed description that follows.
[0008] The implementation of this disclosure can be described in light of the following embodiments, the features of which can be combined in any reasonable manner.
[0009] Implementation Scheme A1. A component comprising: a first thermal module, the first thermal module including one or more thermal components, wherein each thermal component of the first thermal module includes a thermal element and a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface and at least one through-hole extending through the thermal block, and wherein the thermal element and the associated thermal block of each thermal component are in thermal contact; a second thermal module, the second thermal module including one or more thermal components, wherein each thermal component of the second thermal module includes a thermal element and a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface and at least one through-hole extending through the thermal element, and wherein the thermal element and the associated thermal block of each thermal component are in thermal contact; The associated thermal blocks are in thermal contact, and each contact surface of the second thermal module is aligned opposite to an associated contact surface of the first thermal module; a thermal module actuator is configured to enable automated relative movement between the first and second thermal modules to vary the distance between the contact surfaces of each thermal component of the second thermal module and the associated contact surfaces of each thermal component of the first thermal module; and an optical fiber is associated with each through-hole of the thermal block extending through each thermal component of the first thermal module to transmit optical signals through each thermal block of the first thermal module.
[0010] Implementation scheme A2. The component according to implementation scheme A1, wherein each thermal block comprises at least one of thermally conductive ceramic and metal.
[0011] Implementation scheme A3. The component according to implementation scheme A1 or A2, wherein each thermal block comprises aluminum.
[0012] Implementation Scheme A4. The component according to any one of Implementation Schemes A1 to A3, further comprising at least one of an optical transmitter and an optical detector, the optical transmitter and the optical detector being optically coupled to the proximal end of each optical fiber, each optical fiber being associated with a through-hole of the thermal block extending through each thermal component of the first thermal module.
[0013] Implementation scheme A5. The component according to any one of implementation schemes A1 to A4, wherein the first thermal module comprises two thermal components, and wherein the second thermal module comprises two thermal components.
[0014] Implementation Scheme A6. The component according to any one of Implementation Schemes A1 to A5, wherein the thermal block of each thermal component of the first thermal module includes at least two through holes extending through the thermal block.
[0015] Implementation Scheme A7. The component according to any one of Implementation Schemes A1 to A6, wherein the thermal element of each thermal component of the first thermal module includes a through-hole, the through-hole being associated with each through-hole of an associated thermal block extending through the first thermal module, and wherein each optical fiber extends through one of the through-holes, the through-hole extending through the thermal element of the first thermal module.
[0016] Implementation scheme A8. The component according to any one of implementation schemes A1 to A7, wherein the through-hole extends through the thermal block of each thermal component of the first thermal module to the contact surface, and wherein the optical fiber associated with each through-hole extends at least partially through or is aligned with the associated through-hole.
[0017] Implementation Scheme A9. The component according to Implementation Scheme A8, wherein each optical fiber extends fully through the associated aperture such that the end of the optical fiber is flush with the contact surface.
[0018] Implementation Scheme A10. The component according to Implementation Scheme A8, wherein each optical fiber extends fully through the associated aperture such that the end of the optical fiber extends above the contact surface of the associated thermal block.
[0019] Implementation Scheme A11. The component according to Implementation Scheme A10, wherein the end of each optical fiber extends 0.05 mm to 0.35 mm above the contact surface.
[0020] Implementation scheme A12. The component according to any one of implementation schemes A1 to A11, wherein the thermal block of each thermal component of the second thermal module has at least one through hole extending through the thermal block, and wherein the component includes an optical fiber associated with each through hole of the thermal block extending through each thermal component of the second thermal module to transmit an optical signal through each thermal block of the second thermal module.
[0021] Implementation Scheme A13. The component according to Implementation Scheme A12 further includes at least one of an optical transmitter and an optical detector, the optical transmitter and the optical detector being optically coupled to the proximal end of each optical fiber, each optical fiber being associated with the through-hole of the thermal block extending through each thermal component of the second thermal module.
[0022] Implementation Scheme A14. The component according to Implementation Scheme A12 or A13, wherein the thermal block of each thermal component of the second thermal module includes at least two through holes extending through the thermal block.
[0023] Implementation Scheme A15. The component according to any one of Implementation Schemes A12 to A14, wherein the thermal element of each thermal component of the second thermal module includes a through-hole, the through-hole being associated with each through-hole of an associated thermal block extending through the second thermal module, and wherein each optical fiber extends through one of the through-holes, the through-hole extending through the thermal element of the second thermal module.
[0024] Implementation Scheme A16. The assembly according to any one of Implementation Schemes A1 to A15, wherein each thermal component of the first thermal module includes a cover disposed above a thermal element and an associated thermal block of the thermal component, wherein the cover has an opening formed therein through which a contact surface of the thermal block is exposed, and wherein each thermal component of the second thermal module includes a cover disposed above a thermal element and an associated thermal block of the thermal component, wherein the cover has an opening formed therein through which a contact surface of the thermal block is exposed.
[0025] Implementation scheme A17. The component according to implementation scheme A16, wherein the cover comprises plastic.
[0026] Implementation scheme A18. The component according to implementation scheme A16 or A17, wherein each cover includes at least one of Ultem® (polyetherimide) and Delrin® (polyoxymethylene (POM)).
[0027] Implementation scheme A19. The component according to any one of implementation schemes A1 to A18, wherein the thermal element of each thermal component of the first thermal module includes a thermoelectric module, and wherein the thermal element of each thermal component of the second thermal module includes a thermoelectric module.
[0028] Implementation scheme A20. The component according to any one of implementation schemes A1 to A19, wherein each thermal component of the second thermal module includes a heat sink, the heat sink includes a plurality of heat sinks, and wherein the thermal element of each thermal component of the second thermal module is in thermal contact with the heat sink.
[0029] Implementation scheme A21. The component according to implementation scheme A20, wherein each heat sink comprises at least one of thermally conductive ceramic and metal.
[0030] Implementation scheme A22. The component according to implementation scheme A20 or A21, wherein each heat sink comprises aluminum.
[0031] Implementation scheme A23. The component according to any one of implementation schemes A20 to A22, further comprising a separate heat sink associated with each thermal component of the second thermal module.
[0032] Implementation scheme A24. The component according to any one of implementation schemes A20 to A23, further comprising a heat sink heater operatively associated with each heat sink.
[0033] Implementation scheme A25. The component according to any one of implementation schemes A1 to A24, further comprising a mounting block, wherein the thermal element of each thermal component of the first thermal module is in thermal contact with the mounting block.
[0034] Implementation Scheme A26. The component according to Implementation Scheme A25, wherein the mounting block comprises at least one of thermally conductive ceramic and metal.
[0035] Implementation scheme A27. The component according to implementation scheme A25 or A26, wherein the mounting block comprises aluminum.
[0036] Implementation scheme A28. The component according to any one of implementation schemes A25 to A27, further comprising a mounting block heater operatively associated with the mounting block.
[0037] Implementation scheme A29. The component according to any one of implementation schemes A25 to A28 further includes a fan, said fan being positioned adjacent to said mounting block.
[0038] Implementation Scheme A30. The component according to Implementation Scheme A1, further comprising: a heat sink associated with the second thermal module, wherein the heat sink includes a plurality of heat sinks, and wherein the thermal element of each thermal component of the second thermal module is in thermal contact with the heat sink; a cover disposed over the thermal element and the associated thermal block of each thermal component of the second thermal module, wherein the cover has an opening extending therein, through which a contact surface of the associated thermal block is exposed; at least two fasteners securing the cover to the heat sink of each thermal component of the second thermal module, each fastener extending through a hole and into the cover of each thermal component of the second thermal module, the hole passing through a portion of the heat sink; and a spring disposed on each of the at least two fasteners between the head of the fastener and the surface of the heat sink of the second thermal module.
[0039] Implementation scheme A31. The component according to implementation scheme A30, wherein the heat sink includes a separate heat sink for each thermal component of the second thermal module.
[0040] Implementation Scheme A32. The component according to Implementation Scheme A30 or Implementation Scheme A31, further comprising: at least two fasteners securing the heat sink of the second thermal module to the attachment structure, each fastener extending through an opening formed in the heat sink and into the attachment structure; and a spring disposed above each of the at least two fasteners securing the heat sink of the second thermal module to the attachment structure between the head of the fastener and the surface of the heat sink of the second thermal module.
[0041] Implementation Scheme A33. The component according to any one of Implementation Schemes A1 and A30 to A32, further comprising: a mounting block associated with the first thermal module, wherein the thermal element of each thermal component of the first thermal module is in thermal contact with the mounting block; a cover disposed over each thermal element of each thermal component of the first thermal module and the associated thermal block, wherein the cover has an opening formed therein through which a contact surface of the thermal block is exposed; at least two fasteners securing the cover of each thermal component of the first thermal module to the mounting block, each fastener extending through a hole and into the cover, the hole passing through a portion of the mounting block; and a spring disposed above each of the at least two fasteners securing the cover of each thermal component of the first thermal module to the mounting block between the head of the fastener and a surface of the mounting block.
[0042] Implementation Scheme A34. The component according to any one of Implementation Schemes A1 to A33, wherein the second thermal module is fixed and the first thermal module is movable, and wherein the thermal module actuator is coupled to the first thermal module and configured to move the first thermal module relative to the second thermal module between a first position and a second position, wherein when the first thermal module is in the second position, the contact surface of each thermal component of the first thermal module is closer to the associated contact surface of each thermal component of the second thermal module than when the first thermal module is in the first position.
[0043] Implementation Scheme A35. The component according to Implementation Scheme A34 further includes a contact detector coupled to the first thermal module and configured to generate a detectable signal when the contact detector contacts a test platform disposed between the first thermal module and the second thermal module as the first thermal module moves from the first position to the second position.
[0044] Implementation Scheme A36. The component according to Implementation Scheme A35 further includes an upper block to which the first thermal module is attached, and a thermal module actuator coupled to the upper block to move the first thermal module between a first position and a second position, wherein the contact detector includes: an optical sensor attached to the upper block and including an optical emitter and an optical receiver spaced apart from the optical emitter; and a plunger including a plunger rod movably disposed within a hole formed through the upper block and configured such that when the contact detector contacts the test platform disposed between the first thermal module and the second thermal module, a portion of the plunger contacts the test platform, and another portion of the plunger is moved to a position between the optical emitter and the optical receiver of the optical sensor to change the optical beam from the optical emitter to the optical receiver.
[0045] Implementation Scheme A37. The component according to any one of Implementation Schemes A34 to A36, wherein the thermal module actuator comprises: a motor fixed to a motor mounting; and a lead screw coupled to the motor and coupled to the first thermal module such that rotation of the lead screw of the motor causes the first thermal module to move relative to the second thermal module from the first position to the second position or from the second position to the first position.
[0046] Implementation Scheme A38. The component according to Implementation Scheme A37, wherein the motor is mounted on a motor mounting plate supported by the motor mounting member, and wherein continued operation of the motor causes the motor mounting plate to separate from the motor mounting member when the first thermal component is moved to the second position by the thermal module actuator.
[0047] Implementation Scheme A39. The component according to Implementation Scheme A38 further includes at least one spring disposed between the motor mounting plate and a portion of the motor mounting member, such that the spring force of each spring increases as the motor mounting plate separates from the motor mounting member.
[0048] Implementation Scheme A40. The assembly according to Implementation Scheme A39, wherein the motor mounting includes: side supports; a top crossbar extending between the side supports; and an intermediate crossbar extending between the side supports at a position spaced apart from the top crossbar, wherein the motor and motor mounting plate are supported on the intermediate crossbar such that when the first thermal assembly is moved to the second position by the thermal module actuator, continued operation of the motor causes the motor mounting plate to separate from the intermediate crossbar and move toward the top crossbar, and wherein the at least one spring comprises two springs arranged between the motor mounting plate and the top crossbar.
[0049] Implementation Scheme A41. The component according to Implementation Scheme A40 further includes: an upper block to which the first thermal module is attached, wherein the lead screw is coupled to the upper block; and a linear bearing disposed between the intermediate crossbar and the upper block.
[0050] Implementation Scheme A42. The component according to any one of Implementation Schemes A1 to A41 further includes a movable tray for supporting the test platform and configured to selectively move between an extended position not located between the first thermal module and the second thermal module and a retracted position located between the first thermal module and the second thermal module.
[0051] Implementation Scheme B1. A method comprising: (A) placing a test platform including a reaction chamber between a first heater and a second heater; (B) automating the movement of the first heater toward the second heater to clamp the reaction chamber between the first heater and the second heater; (C) applying thermal energy to or absorbing thermal energy from a reaction mixture contained in the reaction chamber clamped between the first heater and the second heater using the first heater and the second heater; and (D) during C, transmitting at least one optical signal through the first heater via an optical fiber embedded in or extending wholly or partially through the first heater.
[0052] Implementation Scheme B2. The method according to Implementation Scheme B1, wherein each of the first heater and the second heater includes a thermal element configured to emit thermal energy to heat a body in thermal contact with the thermal element and / or absorb thermal energy to cool a body in thermal contact with the thermal element, and wherein the optical fiber extends at least partially through an aperture formed through the thermal element.
[0053] Implementation Scheme B3. The method according to Implementation Scheme B2, wherein the thermal element includes a thermoelectric device.
[0054] Implementation Scheme B4. The method according to Implementation Scheme B2 or B3, wherein each of the first heater and the second heater includes a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface that contacts the reaction chamber sandwiched between the first heater and the second heater.
[0055] Implementation Scheme B5. The method according to Implementation Scheme B4, wherein each thermal block comprises at least one of thermally conductive ceramic and metal.
[0056] Implementation Scheme B6. The method according to Implementation Scheme B4 or B5, wherein each thermal block comprises aluminum.
[0057] Implementation Scheme B7. The method according to any one of Implementation Schemes B4 to B6, wherein the hole extends through the thermal block to the contact surface, and wherein the optical fiber at least partially passes through the hole extension extending through the thermal block, or is aligned with the hole extending through the thermal block.
[0058] Implementation Scheme B8. The method according to Implementation Scheme B7, wherein the optical fiber extends completely through the aperture such that the end of the optical fiber is flush with the contact surface, and the aperture extends through the heat block.
[0059] Implementation Scheme B9. The method according to Implementation Scheme B7, wherein the optical fiber extends completely through the aperture such that the end of the optical fiber extends above the contact surface, and the aperture extends through the thermal block.
[0060] Implementation Scheme B10. The method according to any one of Implementation Schemes B4 to B9, wherein each of the first heater and the second heater includes a shroud placed over the thermal element and the associated thermal block, wherein the shroud has an opening formed therein through which the contact surface of the thermal block is exposed.
[0061] Implementation Scheme B11. The method according to Implementation Scheme B10, wherein the cover comprises plastic.
[0062] Implementation Scheme B12. The method according to Implementation Scheme B10 or B11, wherein each hood comprises at least one of Ultem® (polyetherimide) and Delrin® (polyoxymethylene (POM)).
[0063] Implementation Scheme B13. The method according to any one of Implementation Schemes B2 to B12, wherein each of the first heater and the second heater includes a heat sink, and wherein the thermal element of each of the first heater and the second heater is in thermal contact with the heat sink.
[0064] Implementation Scheme B14. The method according to Implementation Scheme B13, wherein the heat dissipation element of at least one of the first heater and the second heater comprises a heat sink.
[0065] Implementation Scheme B15. The method according to Implementation Scheme B13 or B14, wherein each heat sink comprises at least one of thermally conductive ceramic and metal.
[0066] Implementation Scheme B16. The method according to any one of Implementation Schemes B13 to B15, wherein each heat sink comprises aluminum.
[0067] Implementation Scheme B17. The method according to any one of Implementation Schemes B1 to B16, wherein D comprises at least one of: transmitting the at least one optical signal from an optical transmitter to the reaction chamber via the optical fiber; and transmitting the at least one optical signal from the reaction chamber to an optical detector via the optical fiber.
[0068] Implementation Scheme B18. The method according to Implementation Scheme B1, wherein each of the first heater and the second heater includes at least two thermal elements configured to emit thermal energy to heat a body in thermal contact with the thermal elements and / or absorb thermal energy to cool a body in thermal contact with the thermal elements, wherein the first heater and the second heater include the same number of thermal elements, and wherein the optical fiber includes an optical fiber that extends at least partially through an aperture formed through each thermal element of the first heater, and each optical fiber is configured to transmit optical signals to and / or from different reaction chambers.
[0069] Implementation Scheme B19. The method according to Implementation Scheme B18, wherein each thermal element includes a thermoelectric device.
[0070] Implementation Scheme B20. The method according to Implementation Scheme B18 or B19, wherein each of the first heater and the second heater includes a thermal block associated with each thermal element, wherein each thermal block has an exposed contact surface that contacts a different reaction chamber or a set of reaction chambers between the first heater and the second heater.
[0071] Implementation Scheme B21. The method according to Implementation Scheme B20, wherein each optical fiber extends at least partially through or is aligned with an aperture formed through the associated thermal block.
[0072] Implementation Scheme B22. The method according to Implementation Scheme B21, wherein each optical fiber extends fully through the associated aperture such that the end of the optical fiber is flush with or extends above the contact surface of the associated thermal block.
[0073] Implementation Scheme B23. The method according to any one of Implementation Schemes B20 to B22, wherein each of the first heater and the second heater includes a shroud placed over each thermal element and the associated thermal block, wherein the shroud has an opening formed therein through which the contact surface of the associated thermal block is exposed.
[0074] Implementation Scheme B24. The method according to Implementation Scheme B1, wherein the optical fiber comprises at least two optical fibers, each optical fiber extending at least partially through an associated aperture formed through the first heater, and configured to transmit optical signals through the first heater to and / or from different reaction chambers of the test platform.
[0075] Implementation Scheme B25. The method according to any one of Implementation Schemes B1 to B24, further comprising: before realizing the automated movement of the first heater toward the second heater to clamp the reaction chamber between the first heater and the second heater, realizing the automated movement of the test platform from a first position never arranged between the first heater and the second heater to a second position between the first heater and the second heater.
[0076] Implementation Scheme B26. The method according to Implementation Scheme B25, wherein automatically moving the test platform from the first position never arranged between the first heater and the second heater to the second position between the first heater and the second heater includes supporting the test platform on a movable tray, and automatically moving the tray and the test platform supported by the tray from the first position never arranged between the first heater and the second heater to the second position between the first heater and the second heater.
[0077] Implementation Scheme B27. The method according to any one of Implementation Schemes B1 to B26, further comprising detecting the presence of a test platform between the first heater and the second heater using a test platform detector, the test platform detector comprising an optical detector and a plunger shaft mounted at a fixed position relative to the first heater, wherein the plunger shaft is movable relative to the optical detector between a first position and a second position, wherein at the first position the plunger shaft is not detected by the optical detector, and at the second position the plunger shaft is detected by the optical detector, and wherein, while automating the movement of the first heater toward the second heater, if the test platform is located between the first heater and the second heater, the plunger shaft will contact the test platform and move from the first position to the second position.
[0078] Implementation Scheme B28. The method according to any one of Implementation Schemes B1 to B27, further comprising: adding a sample to a sample chamber of the test platform before (A); and combining the sample with one or more other substances contained in one or more chambers of the test platform to form the reaction mixture after (B) and before (C); and wherein (D) comprises transmitting an optical signal from the reaction mixture in the reaction chamber to an optical detector via the optical fiber.
[0079] Implementation Scheme C1. A system for performing a determination, the system comprising: a test platform including at least one reaction chamber for containing a reaction mixture; and an instrument for applying thermal energy to the reaction chamber of the test platform and for transmitting optical signals to and / or from the reaction chamber, the instrument comprising: a first heater and a second heater arranged in a opposed, spaced-apart configuration to receive the reaction chamber between the first heater and the second heater; an actuator for moving the first heater relative to the second heater to clamp the reaction chamber between the first heater and the second heater by moving the first heater toward the second heater and / or by moving the second heater toward the first heater when the reaction chamber is arranged between the first heater and the second heater, wherein the first heater and the second heater apply thermal energy to or absorb thermal energy from the reaction chamber clamped between the first heater and the second heater; and an optical fiber extending at least partially through an opening extending through the first heater and configured to transmit optical signals through the first heater to and / or from the reaction chamber.
[0080] Implementation Scheme C2. The system according to Implementation Scheme C1, wherein each of the first heater and the second heater includes a thermal element configured to emit thermal energy to heat a body in thermal contact with the thermal element and / or absorb thermal energy to cool a body in thermal contact with the thermal element, and wherein the optical fiber extends at least partially through an aperture formed through the thermal element.
[0081] Implementation Scheme C3. The system according to Implementation Scheme C2, wherein the thermal element includes a thermoelectric device.
[0082] Implementation Scheme C4. The system according to Implementation Scheme C2 or C3, wherein each of the first heater and the second heater includes a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface that is in thermal contact with the reaction chamber sandwiched between the first heater and the second heater.
[0083] Implementation Scheme C5. The system according to Implementation Scheme C4, wherein the contact surface is in physical contact with the reaction chamber sandwiched between the first heater and the second heater.
[0084] Implementation Scheme C6. The system according to Implementation Scheme C4 or C5, wherein each thermal block comprises at least one of thermally conductive ceramic and metal.
[0085] Implementation scheme C7. The component according to any one of implementation schemes C4 to C6, wherein each thermal block comprises aluminum.
[0086] Implementation Scheme C8. The system according to any one of Implementation Schemes C4 to C7, wherein the optical fiber extends at least partially through or is aligned with a hole that extends through the thermal block to the contact surface.
[0087] Implementation Scheme C9. The system according to any one of Implementation Schemes C4 to C8, wherein each of the first heater and the second heater includes a shroud placed over the thermal element and the associated thermal block, wherein the shroud has an opening formed therein through which the contact surface of the thermal block is exposed.
[0088] Implementation Scheme C10. The system according to Implementation Scheme C9, wherein the contact surface of the heat block extends above the cover.
[0089] Implementation Scheme C11. The system according to Implementation Scheme C10, wherein the cover comprises plastic.
[0090] Implementation Scheme C12. The system according to any one of Implementation Schemes C9 to C11, wherein each hood comprises at least one of Ultem® (polyetherimide) and Delrin® (polyoxymethylene (POM)).
[0091] Implementation Scheme C13. The system according to any one of Implementation Schemes C2 to C12, wherein each of the first heater and the second heater includes a heat sink, and wherein the thermal element of each of the first heater and the second heater is in thermal contact with the heat sink.
[0092] Implementation Scheme C14. The system according to Implementation Scheme C13, wherein the heat dissipation element of at least one of the first heater and the second heater comprises a heat sink.
[0093] Implementation scheme C15. The system according to implementation scheme C13 or C14, wherein each heat sink comprises at least one of thermally conductive ceramic and metal.
[0094] Implementation scheme C16. The component according to any one of implementation schemes C13 to C15, wherein each heat sink comprises aluminum.
[0095] Implementation Scheme C17. The system according to any one of Implementation Schemes C1 to C16, wherein the instrument includes at least one of an optical transmitter and an optical detector, the optical detector being optically coupled to the proximal end of the optical fiber.
[0096] Implementation Scheme C18. The system according to Implementation Scheme C1, wherein each of the first heater and the second heater includes at least two thermal elements configured to emit thermal energy to heat a body in thermal contact with the thermal elements and / or absorb thermal energy to cool a body in thermal contact with the thermal elements, wherein the first heater and the second heater include the same number of thermal elements, and wherein the optical fiber includes an optical fiber that extends at least partially through an aperture formed through each thermal element of the first heater, and each optical fiber is configured to transmit optical signals to and / or from different reaction chambers.
[0097] Implementation Scheme C19. The system according to Implementation Scheme C18, wherein the instrument includes a plurality of optical fibers that extend at least partially through each thermal element of the first heater.
[0098] Implementation scheme C20. The system according to implementation scheme C18 or C19, wherein each thermal element includes a thermoelectric device.
[0099] Implementation Scheme C21. The system according to Implementation Scheme C19 or C20, wherein each of the first heater and the second heater includes a thermal block associated with each thermal element, wherein each thermal block has an exposed contact surface that contacts a different reaction chamber between the first heater and the second heater.
[0100] Implementation Scheme C22. The system according to Implementation Scheme C21, wherein each optical fiber extends at least partially through or is aligned with an associated aperture that extends through the associated thermal block to the contact surface.
[0101] Implementation Scheme C23. The system according to Implementation Scheme C22, wherein each optical fiber extends fully through the associated aperture such that the end of the optical fiber is flush with the contact surface, or such that the end of the optical fiber extends above the contact surface, the associated aperture extending through the heat block.
[0102] Implementation Scheme C24. The system according to Implementation Scheme C23, wherein the end of each optical fiber extends 0.05 mm to 0.35 mm above the contact surface.
[0103] Implementation Scheme C25. The method according to any one of Implementation Schemes C21 to C24, wherein each of the first heater and the second heater includes a shroud placed over each thermal element and the associated thermal block, wherein the shroud has an opening formed therein through which the contact surface of the associated thermal block is exposed.
[0104] Implementation Scheme C26. The system according to Implementation Scheme C25, wherein the contact surface of each thermal block extends over the associated shroud.
[0105] Implementation Scheme C27. The system according to Implementation Scheme C25 or C26, wherein each hood comprises at least one of Ultem® (polyetherimide) and Delrin® (polyoxymethylene (POM)).
[0106] Implementation Scheme C28. The system according to Implementation Scheme C1, wherein the optical fiber of the instrument comprises at least two optical fibers, each optical fiber extending at least partially through an associated aperture formed through the first heater, and configured to transmit optical signals through the first heater to and / or from different reaction chambers of the test platform.
[0107] Implementation Scheme C29. The system according to any one of Implementation Schemes C1 to C28, wherein the instrument further includes a test platform detector, the test platform detector including an optical detector and a plunger shaft mounted in a fixed position relative to the first heater, wherein the plunger shaft is movable relative to the optical detector between a first position and a second position, wherein at the first position the plunger shaft is not detected by the optical detector, and at the second position the plunger shaft is detected by the optical detector, and wherein, when the first heater is moved relative to the second heater by the actuator, if the test platform is located between the first heater and the second heater, the plunger shaft will contact the test platform and move from the first position to the second position.
[0108] Implementation Scheme C30. The system according to any one of Implementation Schemes C1 to C29, wherein the test platform includes a fluid chamber comprising: a sample chamber for receiving a fluid sample; one or more functional chambers containing materials used in performing the determination; a syringe body; a syringe stop disposed within the syringe body and engageable by a syringe plunger of the instrument; and a channel network connecting the sample chamber and each functional chamber directly or indirectly to the syringe body and connecting the syringe body directly or indirectly to the at least one reaction chamber.
[0109] Implementation Scheme C31. The system according to Implementation Scheme C30, wherein the instrument comprises: a movable tray for supporting the fluid cartridge and configured to move the fluid cartridge supported by the tray between a first position and a second position, wherein in the first position the at least one reaction chamber is not arranged between the first heater and the second heater, and in the second position the at least one reaction chamber is arranged between the first heater and the second heater; and an injection plunger configured to engage with an injection stop to removably connect the injection stop to the end of the injection plunger, and wherein the injection plunger is located within the instrument such that when the cartridge is in the second position the injection plunger is aligned with the injection cartridge body.
[0110] Implementation Scheme C32. The system according to Implementation Scheme C31, wherein the fluid cartridge includes: a process valve associated with each of the sample chamber and one or more functional chambers, the one or more functional chambers containing materials used in performing the determination; and at least two reaction valves associated with each reaction chamber, and wherein the instrument includes: a support bracket on which the fluid cartridge is operatively supported when the fluid cartridge is in the second position; and a plurality of actuator heads disposed within the support bracket, each actuator head being selectively movable relative to the support bracket to engage one of the associated process valves or reaction valves of the fluid cartridge to open or close the associated valve.
[0111] Implementation Scheme C33. The system according to Implementation Scheme C31 or C32, wherein the instrument includes a syringe driver, the syringe driver including a motor, the motor being coupled to the syringe plunger and configured to actuate the syringe plunger.
[0112] Implementation Scheme C34. The system according to Implementation Scheme C33, wherein the instrument includes an encoder and a controller, the encoder being coupled to a motor of the syringe driver, the controller being programmed to control the operation of the syringe driver in the following manner: (A) operating the motor in a first direction to move the syringe plunger and a stop of the syringe plunger coupled to the syringe barrel toward the bottom wall of the syringe barrel; (B) monitoring a motor demand signal of the motor while operating the motor in the first direction, wherein the motor demand includes motor operating parameters directly or indirectly proportional to the motor output; (C) detecting a bend in the motor demand signal, wherein the bend in the motor demand signal indicates that the stop has contacted the bottom wall of the syringe barrel; (D) after detecting the bend, continuing to operate the motor in the first direction until the motor stalls; (E) after detecting the bend and until the motor stalls, counting the encoder steps of the encoder coupled to the motor; (F) (G) After (F), the motor is operated in the second direction to the encoder step counted in E; and (G) the motor is continued to be operated in the second direction to the encoder step count predetermined to move the stop to a predetermined distance away from the bottom wall of the injection barrel to draw a predetermined volume of fluid into the injection barrel body.
[0113] Implementation Scheme C35. The system according to any one of Implementation Schemes C30 to C34, wherein the fluid cartridge includes a syringe stopper removably coupled to the syringe body and configured to hold the syringe stopper against the bottom wall of the syringe body.
[0114] Implementation plan C36. According to the system of embodiment C30, the instrument includes: a syringe plunger configured to engage with a syringe stop to removably connect the syringe stop to the end of the syringe plunger; and a syringe driver including a motor coupled to the syringe plunger and configured to actuate the syringe plunger to move the syringe plunger into the syringe body to engage the stop; and wherein the fluid cartridge includes: a syringe plug removably coupled to the syringe body and configured to hold the syringe stop against the bottom wall of the syringe body, and wherein the syringe plunger and the syringe plug are cooperatively configured such that when the syringe plunger moves into the syringe body, the syringe plunger operatively engages the syringe plug to disengage the syringe plug from the syringe body and allow the syringe stop to move away from the bottom wall of the syringe plunger.
[0115] Implementation Scheme C37. The system according to Implementation Scheme C36, wherein the syringe plunger engages the stop with an interference fit.
[0116] Implementation Scheme C38. The system according to Implementation Scheme C36 or C37, wherein the syringe plunger includes a plunger rib and the syringe plug includes a cam wall, each cam wall having a cam edge, wherein the plunger rib engages the cam edge when the syringe plunger moves into the syringe body to rotate the syringe plug from a first position coupled to the syringe body to a second position disengaged from the syringe body.
[0117] Implementation Scheme C39. The system according to Implementation Scheme C38, wherein the syringe plug includes a flange, and the fluid cartridge includes a plug ring attached to the syringe body, the plug ring including a radial flange, and wherein when the syringe plug is in a first position coupled to the syringe body, the flange of the syringe plug overlaps with the radial flange of the plug ring, and when the syringe plug is in a second position disengaged from the syringe body, the flange of the syringe plug does not overlap with the radial flange of the plug ring.
[0118] Implementation Scheme C40. The system according to any one of Implementation Schemes C30 to C39, wherein the fluid cartridge includes a sample chamber cap for closing the sample chamber, wherein the sample chamber cap includes an upper portion and a lower portion, the lower portion having a radial wall separating the upper portion and the lower portion, wherein the upper portion includes a peripheral wall defined by an axially extending ring protruding above the radial wall, and the lower portion includes a peripheral wall defined by an axially extending tapered wall protruding below the radial wall; wherein a vent is formed in the radial wall and at least one side vent is formed in the peripheral wall of the upper portion, and wherein the lower portion includes at least one radial rib protruding from the outer surface of the tapered wall.
[0119] Implementation Scheme C41. The system according to any one of Implementation Schemes C30 to C40, wherein the fluid cartridge includes a protective vent hood, the protective vent hood being disposed at least over the one or more functional chambers containing the material used in performing the measurement, the protective vent hood comprising: a vent membrane configured to contain fluid in the one or more functional chambers and having through-holes formed therein to allow vapor to pass through the vent membrane; and a protective shield fixed to the vent membrane to block the through-holes and reduce or prevent vapor passage, wherein the protective shield can be peeled off from the vent membrane by a user before using the cartridge.
[0120] Implementation Scheme C42. The system according to Implementation Scheme C41, wherein the venting membrane of the venting hood includes blind tube holes that partially extend through the thickness of the venting membrane.
[0121] Implementation Scheme C43. The system according to any one of Implementation Schemes C30 to C42, wherein the fluid cartridge includes a functional compartment comprising a purification column configured to bind target nucleic acids from the fluid sample material.
[0122] Implementation Scheme C44. The system according to Implementation Scheme C43, wherein the purification column comprises silica.
[0123] Implementation Scheme C45. The system according to any one of Implementation Schemes C30 to C44, wherein the fluid cartridge comprises: a cartridge body having a first side, a second side, at least one opening in the cartridge body extending from the first side to the second side, and one or more grooves formed in the second side; a first film attached to the first side of the cartridge body and covering a first end of the at least one opening, wherein the first film comprises a transparent or translucent material to allow optical signals to pass through the first film into or out of the at least one opening; and a second film attached to the second side of the cartridge body and covering the one or more grooves to form a portion of the second side. One or more channels, wherein the second film covers a portion of the second surface spatially separated from the at least one opening; and a thermally conductive laminated seal attached to the second surface of the box body and covering the second end of the at least one opening, wherein the at least one opening covered by the first film and the thermally conductive laminated seal defines a reaction chamber for receiving the reaction mixture, wherein the thermally conductive laminated seal comprises: a plastic layer attached to the second surface of the box body and covering the second end of the at least one opening; and a conductive foil layer attached to the surface of the plastic layer opposite to the surface of the plastic attached to the second surface of the box body.
[0124] Implementation Scheme C46. The system according to Implementation Scheme C45, wherein the box body includes one or more grooves formed in the first surface, and wherein the one or more grooves formed in the first surface are covered by the first film attached to the first surface of the box body to form one or more channels traversing a portion of the first surface.
[0125] Implementation Scheme C47. The system according to Implementation Scheme C45 or C46, wherein the second film includes a cutout exposing the at least one opening, and wherein the thermally conductive laminated seal is attached to a second side of the housing body within the cutout of the second film.
[0126] Implementation Scheme C48. The system according to any one of Implementation Schemes C45 to C47, wherein the plastic layer comprises polypropylene.
[0127] Implementation Scheme C49. The system according to any one of Implementation Schemes C45 to C48, wherein the conductive layer comprises a metal foil.
[0128] Implementation Scheme C50. The system according to Implementation Scheme C49, wherein the metal foil comprises aluminum.
[0129] Implementation Scheme C51. The system according to any one of Implementation Schemes C45 to C50, wherein the conductive layer is reflective and the plastic layer is transparent or translucent.
[0130] Implementation Scheme C52. The system according to any one of Implementation Schemes C45 to C51, wherein the box body is opaque.
[0131] Implementation scheme C53. The system according to any one of implementation schemes C45 to C52, wherein the thickness of the plastic layer of the thermally conductive laminated seal is less than the thickness of the second film.
[0132] Implementation scheme C54. The system according to any one of implementation schemes C45 to C53, wherein the thickness of the plastic layer is about 10 µm to about 20 µm.
[0133] Implementation Scheme C55. The system according to any one of Implementation Schemes C45 to C54, wherein the thickness of the conductive layer is about 60 µm to about 80 µm.
[0134] Implementation Scheme C56. The system according to any one of Implementation Schemes C45 to C55, wherein the thickness of the second film is about 100 µm to about 200 µm.
[0135] Implementation Scheme C57. The system according to any one of Implementation Schemes C45 to C56, wherein the second film comprises polypropylene.
[0136] Implementation scheme C58. The system according to any one of implementation schemes C45 to C57, wherein the first surface is the top surface of the box and the second surface is the bottom surface of the box.
[0137] Implementation Scheme C59. The system according to any one of Implementation Schemes C45 to C58, wherein the box body is plastic, and the thermally conductive laminated seal is attached to a second side of the box body by heat sealing or ultrasonic welding between the plastic layer and the box body.
[0138] Implementation scheme C60. The system according to any one of implementation schemes C45 to C58, wherein the thermally conductive laminated seal is attached to the second side of the housing body by an adhesive.
[0139] Implementation Scheme C61. The system according to any one of Implementation Schemes C45 to C60, wherein the housing body includes at least two openings adjacent to each other, the at least two openings extending from a first surface to a second surface, a first film covering the first end of each of the at least two openings, and a thermally conductive laminated seal covering the end of each of the at least two openings, wherein the thermally conductive laminated seal is configured and arranged to minimize or prevent optical transmission between the at least two openings through a plastic layer of the thermally conductive laminated seal.
[0140] Implementation Scheme C62. The system according to any one of claims C32 to C34, further comprising: a first actuation mechanism configured to selectively move each of the plurality of actuator heads relative to the support bracket to engage said associated one of the process valves of the fluid cartridge to open or close said associated process valve, wherein said plurality of process valves are arranged in a circular configuration. The first actuation mechanism includes a valve actuator piston operably engageable with each of the plurality of actuator heads associated with one of the process valves, wherein each valve actuator piston extends into or through the support bracket and is movable between a first position and a second position, the first position corresponding to one of a closed configuration of the process valve associated with the engaged actuator head and an open position of the process valve associated with the engaged actuator head, and the second position corresponding to the other of an open position of the process valve associated with the engaged actuator head and a closed position of the process valve associated with the engaged actuator head. A spring is coupled to each valve actuator piston to bias the valve actuator piston into the first position. A cam follower surface is associated with each valve actuator piston. A rotary cam is rotatable about a rotation axis corresponding to the center of the circular configuration of the plurality of process valves, and the rotary cam includes a cam rod and a cam, the cam rod extending radially relative to and rotatable about the rotation axis, and the cam being disposed on the radially outer end of the cam rod. Rotation of the cam rod about the rotation axis causes the cam to engage the cam follower surface associated with each valve actuator piston one at a time, so that the valve actuator piston associated with the cam follower surface engaged by the cam moves from the first position to the second position.
[0141] Implementation Scheme C63. The system according to any one of embodiments C32 to C34 and C62 further includes a second actuation mechanism configured to selectively move each of the plurality of actuator heads relative to the support bracket to engage said associated one of the reaction valves of the fluid cartridge to open or close said associated reaction valve. The second actuation mechanism includes a valve actuator piston operably engageable with each of the plurality of actuator heads associated with one of the reaction valves, wherein each valve actuator piston is movable between a first position and a second position, the first position corresponding to one of a closed configuration and an open position of the engaged reaction valve, and the second position corresponding to the other of an open position and a closed position of the engaged reaction valve. A spring is coupled to each valve actuator piston for biasing the valve actuator piston to the first position. At least one camshaft is supported for rotation about a camshaft rotation axis and includes at least one cam lob. An actuator lever is associated with each cam lobe and each valve actuator piston, and is oriented transversely to the longitudinal axis of the camshaft. The actuator lever includes a pivot connection at which it is mounted for pivoting about a pivot axis; a piston engagement spatially separated from the pivot connection, at which the actuator lever is operatively engaged with the associated valve actuator piston, such that pivoting of the actuator lever about the pivot axis in a first direction moves the associated valve actuator piston from its first position to its second position; and a cam follower surface disposed between the pivot connection and the piston engagement. The cam follower surface is configured and arranged to engage with the associated cam lobe as the camshaft rotates about its axis of rotation, causing pivoting movement of the actuator lever in the first direction.
[0142] Implementation Scheme C64. The system according to any one of Implementation Schemes C45 to C61 further includes a drying agent that is adhered to the outer surface of the plastic layer of the thermally conductive laminated seal.
[0143] Implementation Scheme C65. The system according to Implementation Scheme C64, wherein the drying reagent is only adhered to a portion of the outer surface of the plastic layer corresponding to the position of the reaction chamber.
[0144] Implementation Scheme C66. The system according to Implementation Scheme C65, wherein the portion of the outer surface of the plastic layer to which the drying agent adheres is treated in order to increase the hydrophilicity of the portion of the outer surface.
[0145] Implementation Scheme C67. The system according to Implementation Scheme C66, wherein the portion of the outer surface of the plastic layer to which the drying agent adheres is treated with corona discharge or plasma treatment to increase the hydrophilicity of the portion of the outer surface.
[0146] Implementation Scheme C68. The system according to Implementation Scheme C59, wherein the housing body includes one or more energy directors formed on the second surface and at least partially surrounding each of the at least one opening, wherein the energy directors are configured to melt and fuse with the plastic layer during a heat-sealing process or an ultrasonic welding process.
[0147] Implementation Scheme C69. The system according to Implementation Scheme C68, wherein the cartridge body includes: one or more inspection holes formed through the cartridge body at the region to which the thermally conductive laminated seal of the fluid cartridge is attached; and an energy director that at least partially surrounds each inspection hole.
[0148] Implementation Scheme C70. A system according to any one of embodiments C30 to C44, wherein the fluid cartridge comprises: a cartridge body having a first side, a second side, one or more openings extending from the first side to the second side, and one or more grooves formed in the second side; a first film attached to the first side of the cartridge body and covering a first end of the one or more openings, wherein the first film comprises a transparent or translucent material to allow optical signals to pass through the first film to or from the one or more openings; a second film attached to the second side of the cartridge body and covering the one or more grooves to form one or more channels traversing a portion of the second side and a second end of each of the one or more openings, wherein the one or more openings covered by the first film and the second film define one or more reaction chambers for receiving the reaction mixture; and one or more drying agents adhered to the surface of the second film, wherein the position of each of the one or more drying agents corresponds to the position of each of the one or more reaction chambers.
[0149] Implementation Scheme C71. The system according to Implementation Scheme C70, wherein the drying reagent is adhered only to the portion of the second film corresponding to the location of the one or more reaction chambers.
[0150] Implementation Scheme C72. The system according to Implementation Scheme C71, wherein the portion of the surface of the second film to which the one or more drying agents adhere is more hydrophilic than the remaining portion of the surface of the second film.
[0151] Implementation D1. An instrument for receiving a fluid cartridge, wherein the fluid cartridge includes a sample chamber and a cap for closing the sample chamber, the instrument comprising: a first frame; a second frame including a cartridge support bracket configured to hold the cartridge between the first frame and the second frame; an actuator coupled to one or both of the first frame and the second frame and configured to enable automated relative movement between the first frame and the second frame to change the distance between the first frame and the second frame; and a cartridge detector mounted within the upper frame, wherein the cartridge detector includes a plunger rod and a sensor, the plunger rod being configured between a first position and a second position, the sensor being configured to detect when the plunger rod is in the second position, and wherein, when the first frame and the second frame move relative to each other via the actuator, if the cartridge is located on the cartridge support bracket, the plunger rod will contact the cartridge and move from the first position to the second position.
[0152] Implementation Scheme D2. The instrument according to Implementation Scheme D1, wherein the sensor of the box detector includes an optical detector, wherein the plunger rod is not detected by the optical detector when the plunger rod is in the first position, and is detected by the optical detector when the plunger rod is in the second position.
[0153] Implementation scheme D3. The instrument according to implementation scheme D1 or D2, wherein the box detector includes a spring connected to the plunger rod to bias the plunger rod into the first position.
[0154] Implementation D4. The instrument according to any one of implementations D1 to D3, wherein the cassette detector includes a plunger pad attached to the end of the plunger rod for contacting the cassette located on the cassette support bracket as the first frame and the second frame move toward each other relative to each other.
[0155] Implementation Scheme D5. The instrument according to Implementation Scheme D4, wherein if the box is located on the box support bracket, the plunger pad will contact the cap when the first frame and the second frame move toward each other relative to each other.
[0156] Implementation Scheme D6. The instrument according to Implementation Scheme D2, wherein the first frame includes an upper block having a through hole through which the plunger rod extends, and wherein the optical detector includes an optical transmitter disposed on one side of the through hole and an optical receiver disposed on the opposite side of the through hole, such that when the plunger rod is moved to the second position, a portion of the plunger rod is positioned between the optical transmitter and the optical receiver to disrupt the optical beam between the optical transmitter and the optical receiver.
[0157] Implementation Scheme D7. The instrument according to any one of Implementation Schemes D1 to D6, wherein the fluid cartridge includes one or more reaction chambers, and wherein the first frame includes a first thermal module configured to apply heat energy to a first side of each of the one or more reaction chambers; the second frame includes a second thermal module configured to apply heat energy to a second side of each of the one or more reaction chambers; and the actuator is controlled to achieve automated relative movement between the first frame and the second frame to selectively position a portion of each of the first thermal module and the second thermal module into thermal contact with the one or more reaction chambers.
[0158] Implementation Scheme D8. The instrument according to Implementation Scheme D7 further includes an optical fiber associated with each of the one or more reaction chambers, wherein each optical fiber extends through a portion of the first thermal module to transmit optical signals through the first thermal module to and / or from the associated reaction chamber.
[0159] Implementation Scheme D9. The instrument according to Implementation Scheme D8 further includes at least one of an optical transmitter and an optical detector optically coupled to the proximal end of each optical fiber extending through the first thermal module.
[0160] Implementation E1. An instrument for applying thermal energy to a reaction chamber of a test platform, the instrument comprising: a first heater and a second heater, the first heater and the second heater being arranged in a spaced-apart configuration to receive the reaction chamber in a position relative to the first heater and the second heater, such that the first heater and the second heater contact different portions of the reaction chamber, and wherein each heater is configured to apply thermal energy to the reaction chamber by conductive heat transfer through a portion of the reaction chamber contacted by the respective heater; a first controller, the first controller being configured to control the thermal energy generated by the first heater; and a second controller, the second controller being configured to control the thermal energy generated by the second heater, wherein the first controller controls the thermal energy generated by the first heater independently of the second controller controlling the thermal energy generated by the second heater, and the second controller controls the thermal energy generated by the second heater independently of the first controller controlling the thermal energy generated by the first heater, and wherein the first controller controls the thermal energy generated by the first heater, and the second controller controls the thermal energy generated by the second heater, to achieve a common temperature distribution for the first heater and the second heater.
[0161] Implementation E2. The instrument according to implementation E1 further includes an actuator for moving the first heater relative to the second heater by moving the first heater toward the second heater to clamp the reaction chamber between the first heater and the second heater when the reaction chamber is arranged between the first heater and the second heater, wherein the first heater and the second heater apply thermal energy to the reaction chamber clamped between the first heater and the second heater.
[0162] Implementation E3. The instrument according to implementation E1 or E2 further includes an optical fiber that extends at least partially through a hole formed through the first heater and is configured to transmit optical signals through and / or from the reaction chamber via the first heater.
[0163] Implementation E4. The instrument according to any one of implementations E1 to E3, wherein each of the first heater and the second heater includes a thermal element configured to emit thermal energy to heat the body in thermal contact with the thermal element and / or absorb thermal energy to cool the body in thermal contact with the thermal element.
[0164] Implementation E5. The instrument according to implementation E3, wherein each of the first heater and the second heater includes a thermal element configured to emit thermal energy to heat a body in thermal contact with the thermal element and / or absorb thermal energy to cool a body in thermal contact with the thermal element, and wherein the optical fiber extends at least partially through an aperture formed through the thermal element of the first heater.
[0165] Implementation scheme E6. The instrument according to implementation scheme E4 or E5, wherein the thermal element includes a thermoelectric device.
[0166] Implementation E7. The instrument according to any one of implementations E4 to E6, wherein each of the first heater and the second heater includes a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface that contacts the reaction chamber arranged between the first heater and the second heater.
[0167] Implementation scheme E8. The instrument according to implementation scheme E7, wherein each thermal block comprises at least one of thermally conductive ceramic and metal.
[0168] Implementation scheme E9. The instrument according to implementation scheme E7 or E8, wherein each hot block comprises aluminum.
[0169] Implementation E10. The instrument according to implementation E5, wherein each of the first heater and the second heater includes a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface that contacts a reaction chamber sandwiched between the first heater and the second heater, and wherein the optical fiber extends at least partially through or aligned with an aperture formed through the first heater to the contact surface.
[0170] Implementation E11. The instrument according to implementation E10, wherein the optical fiber extends completely through the associated aperture such that the end of the optical fiber is flush with the contact surface, or the end of the optical fiber extends above the contact surface of the associated thermal block.
[0171] Implementation E12. The instrument according to any one of implementations E7 to E11, wherein each of the first heater and the second heater includes a shroud placed over the thermal element and the associated thermal block, wherein the shroud has an opening formed therein through which the contact surface of the thermal block is exposed.
[0172] Implementation scheme E13. The instrument according to implementation scheme E12, wherein the cover comprises plastic.
[0173] Implementation scheme E14. The instrument according to implementation scheme E12 or E13, wherein each hood comprises at least one of Ultem® (polyetherimide) and Delrin® (polyoxymethylene (POM)).
[0174] Implementation E15. The instrument according to any one of implementations E4 to E14, wherein each of the first heater and the second heater includes a heat sink, and wherein the thermal element of each of the first heater and the second heater is in thermal contact with the heat sink.
[0175] Implementation E16. The instrument according to implementation E15, wherein the heat dissipation element of at least one of the first heater and the second heater comprises a heat sink.
[0176] Implementation scheme E17. The instrument according to implementation scheme E16, wherein each heat sink comprises at least one of thermally conductive ceramic and metal.
[0177] Implementation scheme E18. The component according to any one of implementation schemes E15 to E17, wherein each heat sink comprises aluminum.
[0178] Implementation E19. The instrument according to any one of embodiments E1 to E18 further includes a movable holder for supporting a test platform and configured to move the test platform supported by the movable holder between a first position where the reaction chamber is not positioned between the first heater and the second heater and a second position where the reaction chamber is positioned between the first heater and the second heater.
[0179] Implementation scheme E20. The instrument according to implementation scheme E3 or E5 further includes at least one of an optical transmitter and an optical detector optically coupled to the proximal end of the optical fiber.
[0180] Implementation E21. An instrument according to any one of embodiments E1 to E20, comprising: a first temperature sensor for monitoring the temperature of a first heater; and a second temperature sensor for monitoring the temperature of a second heater, wherein the first temperature sensor and the second temperature sensor are independent of each other, wherein a first controller is configured to control the heat energy generated by the first heater by comparing a temperature measurement of the first heater from the first temperature sensor with a common temperature distribution, and to apply power to the first heater in response to the comparison of the temperature measurement from the first temperature sensor with the common temperature distribution, and wherein the second controller is configured to control the heat energy generated by the second heater by comparing a temperature measurement of the second heater from the second temperature sensor with the common temperature distribution, and to apply power to the second heater in response to the comparison of the temperature measurement from the second temperature sensor with the common temperature distribution.
[0181] Implementation F1. A method for applying thermal energy to a reaction chamber of a test platform, the method comprising: applying thermal energy to a first side and a second side of the reaction chamber using a first heater and a second heater, respectively; controlling the thermal energy generated by the first heater independently of the thermal energy generated by the second heater; controlling the thermal energy generated by the second heater independently of the thermal energy generated by the first heater; and controlling the thermal energy generated by the first heater and the thermal energy generated by the second heater to achieve a common temperature distribution for the first heater and the second heater.
[0182] Implementation F2. The method according to implementation F1 further includes, when the reaction chamber is arranged between the first heater and the second heater, using an actuator to move the first heater relative to the second heater to clamp the reaction chamber between the first heater and the second heater by moving the first heater toward the second heater, and using the first heater and the second heater to apply thermal energy to the reaction chamber clamped between the first heater and the second heater.
[0183] Implementation F3. The method according to implementation F1 or F2 further includes transmitting an optical signal through the first heater to and / or from the reaction chamber using an optical fiber, the optical fiber extending through at least a portion of the first heater.
[0184] Implementation scheme F4. The method according to any one of implementation schemes F1 to F3, wherein each of the first heater and the second heater includes a thermal element configured to emit thermal energy to heat the body in thermal contact with the thermal element and / or absorb thermal energy to cool the body in thermal contact with the thermal element.
[0185] Implementation F5. The method according to implementation F3, wherein each of the first heater and the second heater includes a thermal element configured to emit thermal energy to heat a body in thermal contact with the thermal element and / or absorb thermal energy to cool a body in thermal contact with the thermal element, and wherein the optical fiber extends at least partially through an aperture formed through the thermal element of the first heater.
[0186] Implementation scheme F6. The method according to implementation scheme F4 or F5, wherein the thermal element includes a thermoelectric device.
[0187] Implementation F7. The method according to any one of implementations F4 to F6, wherein applying thermal energy to a first side and a second side of the reaction chamber using the first heater and the second heater comprises: contacting the first side of the reaction chamber with a contact surface of a hot block associated with a hot element of the first heater; and contacting the second side of the reaction chamber with a contact surface of a hot block associated with a hot element of the second heater.
[0188] Implementation F8. The method according to implementation F5, wherein each of the first heater and the second heater includes a thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface that contacts a reaction chamber sandwiched between the first heater and the second heater, and wherein the optical fiber extends at least partially through or aligned with a hole formed through the first heater to the contact surface.
[0189] Implementation F9. The method according to any one of implementations F1 to F8, further comprising moving the test platform between a first position and a second position, wherein in the first position the reaction chamber is not arranged between the first heater and the second heater, and in the second position the reaction chamber is arranged between the first heater and the second heater, wherein moving the test platform between the first position and the second position is achieved by powered movement of a tray supporting the test platform.
[0190] Implementation F10. A method according to any one of implementations F1 to F9, wherein controlling the heat energy generated by the first heater to achieve the common temperature distribution comprises: monitoring the temperature of the first heater using a first temperature sensor; comparing the temperature measurement of the first heater from the first temperature sensor with the common temperature distribution; applying power to the first heater in response to the comparison of the temperature measurement from the first temperature sensor with the common temperature distribution; monitoring the temperature of the second heater using a second temperature sensor; comparing the temperature measurement of the second heater from the second temperature sensor with the common temperature distribution; and applying power to the second heater in response to the comparison of the temperature measurement from the second temperature sensor with the common temperature distribution, wherein the first temperature sensor and the second temperature sensor are independent of each other.
[0191] Implementation Scheme G1. A method for controlling an injection pump, the injection pump including an elastomeric stop disposed within an injection barrel and an injection barrel plunger connected to the stop, the method comprising: (A) operating a motor coupled to the injection barrel plunger in a first direction to move the injection barrel plunger and the stop within the injection barrel toward a bottom wall of the injection barrel; (B) monitoring a motor demand signal of the motor while operating the motor in the first direction, wherein the motor demand includes motor operating parameters directly or indirectly proportional to the motor output; (C) detecting a deflection in the motor demand signal, wherein the deflection in the motor demand signal indicates that the stop has contacted the bottom wall of the injection barrel; (D) after detecting the deflection, continuing to operate the motor in the first direction until the motor stalls; (E) after detecting the deflection and until the motor stalls, counting encoder steps of an encoder coupled to the motor; (F) operating the motor in a second direction until (E). The encoder step count is counted in the middle; and (G) after (F), the motor continues to be operated in the second direction to move the stop away from the bottom wall of the injection cylinder by a predefined distance to draw a predefined volume of fluid into the injection cylinder body.
[0192] Implementation scheme G2. The method according to implementation scheme G1, wherein the motor requirement includes at least one of the motor requirement current, the motor requirement voltage, and the motor requirement power.
[0193] Implementation scheme G3. The method according to implementation scheme G1 or G2, wherein G includes operating the motor in the second direction to a predetermined number of steps of the encoder.
[0194] Implementation scheme G4. The method according to any one of implementation schemes G1 to G3, wherein the motor includes a servo motor.
[0195] Implementation scheme G5. The method according to any one of implementation schemes G1 to G4, wherein the encoder comprises a rotary encoder.
[0196] Implementation scheme G6. The method according to any one of implementation schemes G1 to G5, wherein D includes detecting motor stall by detecting from the encoder that the motor has stopped rotating and / or by detecting that the motor demand has reached a predefined maximum level.
[0197] Implementation scheme G7. The method according to any one of implementation schemes G1 to G6, wherein the syringe plunger is a component of the instrument, and the stop is a component of a fluid cartridge acted upon by the instrument, and wherein the syringe body is defined by a sidewall of a chamber of the fluid cartridge in fluid communication with other chambers of the cartridge.
[0198] Implementation scheme G8. The method according to implementation scheme G7, wherein the stop is retained in the syringe barrel by a blocking member, the blocking member being releasably interlocked with a side wall defining the chamber of the syringe barrel, wherein when the syringe plunger is inserted through the blocking member and engages with the stop, the blocking member is released by the syringe plunger to allow the stop to move vertically during use.
[0199] Implementation scheme G9. The method according to any one of implementation schemes G1 to G8, wherein the syringe plunger engages the stop with an interference fit.
[0200] Implementation Scheme H1. A cartridge for detecting an analyte of interest from a reaction mixture by exposing the reaction mixture to an excitation optical signal and detecting the presence or absence of an emission optical signal from the reaction mixture, the cartridge comprising: a cartridge body having a first surface, a second surface, at least one opening in the cartridge body extending from the first surface to the second surface, and one or more grooves formed in the second surface; a first film attached to the first surface of the cartridge body and covering a first end of the at least one opening, wherein the first film comprises a transparent or translucent material to allow an optical signal to pass through the first film into or out of the at least one opening; and a second film attached to a second surface of the cartridge body and covering the one or more grooves. A plurality of grooves to form one or more channels traversing a portion of the second surface, wherein the second film covers a portion of the second surface spatially separated from the at least one opening; and a thermally conductive laminated seal attached to the second surface of the housing body and covering a second end of the at least one opening, wherein the at least one opening covered by the first film and the thermally conductive laminated seal defines a reaction chamber for receiving the reaction mixture, wherein the thermally conductive laminated seal comprises: a plastic layer attached to the second surface of the housing body and covering a second end of the at least one opening; and a conductive layer attached to a surface of the plastic layer opposite to the surface of the plastic attached to the second surface of the housing body.
[0201] Implementation H2. The box according to implementation H1, wherein the box body includes one or more grooves formed in the first surface, and wherein the one or more grooves formed in the first surface are covered by the first film attached to the first surface of the box body to form one or more channels traversing a portion of the first surface.
[0202] Implementation H3. The box according to implementation H1 or H2, wherein the second film includes a cutout exposing the at least one opening, and wherein the thermally conductive laminated seal is attached to a second side of the box body within the cutout of the second film.
[0203] Implementation scheme H4. The box according to any one of implementation schemes H1 to H3, wherein the plastic layer comprises polypropylene.
[0204] Implementation scheme H5. The box according to any one of implementation schemes H1 to H4, wherein the conductive layer comprises a metal foil.
[0205] Implementation scheme H6. The box according to implementation scheme H5, wherein the metal foil comprises aluminum.
[0206] Implementation Scheme H7. The box according to any one of Implementation Schemes H1 to H6, wherein the conductive layer is reflective and the plastic layer is transparent or translucent.
[0207] Implementation scheme H8. A box according to any one of implementation schemes H1 to H7, wherein the box body is opaque.
[0208] Implementation scheme H9. The box according to any one of implementation schemes H1 to H8, wherein the thickness of the plastic layer of the thermally conductive laminated seal is less than the thickness of the second film.
[0209] Implementation scheme H10. The box according to any one of implementation schemes H1 to H9, wherein the thickness of the plastic layer is about 10 µm to about 20 µm.
[0210] Implementation H11. The box according to any one of Implementations H1 to H10, wherein the thickness of the conductive layer is about 60 µm to about 80 µm.
[0211] Implementation Scheme H12. The box according to any one of Implementation Schemes H1 to H11, wherein the thickness of the second film is about 100 µm to about 200 µm.
[0212] Implementation Scheme H13. The box according to any one of Implementation Schemes H1 to H12, wherein the second film comprises polypropylene.
[0213] Implementation scheme H14. A box according to any one of implementation schemes H1 to H13, wherein the first side is the top surface of the box and the second side is the bottom surface of the box.
[0214] Implementation Scheme H15. A box according to any one of Implementation Schemes H1 to H14, wherein the box body is plastic, and the thermally conductive laminated seal is attached to a second side of the box body by heat sealing or ultrasonic welding between the plastic layer and the box body.
[0215] Implementation scheme H16. The box according to any one of implementation schemes H1 to H14, wherein the thermally conductive laminated seal is attached to the second side of the box body by an adhesive.
[0216] Implementation H17. A box according to any one of embodiments H1 to H16, wherein the box body includes at least two openings adjacent to each other, the at least two openings extending from a first surface to a second surface, a first film covering the first end of each of the at least two openings, and a thermally conductive laminated seal covering the end of each of the at least two openings, wherein the thermally conductive laminated seal is configured and arranged to minimize or prevent optical transmission between the at least two openings through a plastic layer of the thermally conductive laminated seal.
[0217] Implementation Scheme H18. A cartridge, wherein the presence or absence of an analyte of interest contained in a reaction mixture can be detected within the cartridge by exposing a reaction mixture to an excitation optical signal and detecting the presence or absence of an emission optical signal from the reaction mixture, the cartridge comprising: a cartridge body having one or more reaction chambers, each reaction chamber being configured to receive a reaction mixture, wherein a wall of each reaction chamber is transparent or translucent to allow an optical signal to enter or exit the reaction chamber through the wall, and wherein each reaction chamber is open to a surface of the cartridge body; a film attached to a surface of the cartridge body and covering a first portion of the surface of the cartridge body. The first portion of the surface is spatially separated from the reaction chamber open to the surface; and a thermally conductive laminated seal is attached to a second portion of the surface of the box body, wherein the second portion of the surface surrounds the reaction chamber open to the surface, and the thermally conductive laminated seal closes the reaction chamber, and wherein the thermally conductive laminated seal comprises: a plastic layer attached to the second portion of the surface of the box body and closing the reaction chamber; and a conductive layer attached to a surface of the plastic layer opposite to the surface of the second portion of the plastic attached to the surface of the box body.
[0218] Implementation Scheme H19. The box according to Implementation Scheme H18, wherein the box body includes a first side and a second side, and wherein the second side surrounds the surface of the box body that is open to the reaction chamber, and wherein the reaction chamber is transparent or translucent, and one wall includes a transparent or translucent film attached to the first side of the box body and covering a first end of the reaction chamber.
[0219] Implementation H20. The box according to implementation H19, wherein the box body includes one or more grooves formed in the first surface, and wherein the one or more grooves formed in the first surface are covered by the film attached to the first surface of the box body to form one or more channels traversing a portion of the first surface.
[0220] Implementation Scheme H21. The box according to any one of Implementation Schemes H18 to H20, wherein the film attached to the surface of the box body opening to the reaction chamber includes a slit, and wherein the thermally conductive laminated seal is attached to the box body within the slit.
[0221] Implementation Scheme H22. The box according to any one of Implementation Schemes H18 to H21, wherein the plastic layer comprises polypropylene.
[0222] Implementation scheme H23. The box according to any one of implementation schemes H18 to H22, wherein the conductive layer comprises a metal foil.
[0223] Implementation scheme H24. The box according to implementation scheme H23, wherein the metal foil comprises aluminum.
[0224] Implementation Scheme H25. The box according to any one of Implementation Schemes H18 to H24, wherein the conductive layer is reflective and the plastic layer is transparent or translucent.
[0225] Implementation Scheme H26. The box according to any one of Implementation Schemes H18 to H25, wherein the thickness of the plastic layer of the thermally conductive laminated seal is less than the thickness of the film attached to the surface of the box body that is open to the reaction chamber.
[0226] Implementation H27. The box according to any one of Implementations H18 to H26, wherein the thickness of the plastic layer is about 10 µm to about 20 µm.
[0227] Implementation H28. The box according to any one of implementations H18 to H27, wherein the thickness of the conductive layer is about 60 µm to about 80 µm.
[0228] Implementation Scheme H29. The box according to Implementation Scheme H19 or H20, wherein the thickness of the film attached to the surface of the box body that is open to the reaction chamber is about 100 µm to about 200 µm.
[0229] Implementation scheme H30. The box according to any one of implementation schemes H18, H20 or H29, wherein the film attached to the surface of the box body that is open to the reaction chamber comprises polypropylene.
[0230] Implementation scheme H31. The box according to implementation schemes H19 to H20, wherein the first side is the top surface of the box and the second side is the bottom surface of the box.
[0231] Implementation scheme H32. A box according to any one of implementation schemes H18 to H31, wherein the box body is plastic, and the thermally conductive laminate is attached to the box body by heat sealing or ultrasonic welding between the plastic layer and the box body.
[0232] Implementation scheme H33. The box according to any one of implementation schemes H18 to H31, wherein the thermally conductive laminated seal is attached to the box by an adhesive.
[0233] Implementation H34. A box according to any one of Implementations H18 to H33, wherein the box body includes at least two reaction chambers, and the thermally conductive laminated seal closes the at least two reaction chambers, and wherein the thermally conductive laminated seal is configured and arranged to minimize or prevent optical transmission between the at least two reaction chambers through the plastic layer of the thermally conductive laminated seal.
[0234] Implementation scheme H35. The box according to any one of implementation schemes H1 to H34 further includes a desiccant, said desiccant being adhered to the outer surface of the plastic layer of the thermally conductive laminated seal.
[0235] Implementation scheme H36. The box according to implementation scheme H35, wherein the drying reagent is only adhered to a portion of the outer surface of the plastic layer corresponding to the position of the reaction chamber.
[0236] Implementation Scheme H37. The box according to Implementation Scheme H36, wherein at least a portion of the surface of the plastic layer is treated such that the portion of the surface to which the drying agent adheres has greater hydrophilicity compared to the remaining portion of the surface of the plastic layer.
[0237] Implementation Scheme H38. The box according to Implementation Scheme H36, wherein the portion to which the drying agent adheres to the outer surface of the plastic layer is treated is made to increase the hydrophilicity of the treated portion of the outer surface of the plastic layer compared to the untreated portion of the outer surface of the plastic layer.
[0238] Implementation Scheme H39. The box according to Implementation Scheme H38, wherein the portion of the outer surface of the plastic layer to which the drying agent adheres is treated with corona discharge or plasma treatment to increase the hydrophilicity of the treated portion of the outer surface of the plastic layer compared to the untreated portion of the outer surface of the plastic layer.
[0239] Implementation H40. The box according to implementation H15 or H32, wherein the box body includes one or more energy directors formed on the second surface and at least partially surrounding each of the at least one opening, wherein the energy directors are configured to melt and fuse with the plastic layer during a heat-sealing process or an ultrasonic welding process.
[0240] Implementation H41. The box according to implementation H40, wherein the box body includes: one or more inspection holes formed through the box body at the region to which the thermally conductive laminated seal of the fluid box is attached; and an energy director that at least partially surrounds each inspection hole.
[0241] Implementation Scheme I1. A system for applying thermal energy to a reaction mixture and transmitting optical signals to and / or from the reaction mixture, the system comprising: a reaction chamber for receiving the reaction mixture, wherein a first wall of the reaction chamber is transparent or translucent, and a second wall of the reaction chamber includes a thermally conductive laminated seal, wherein the thermally conductive laminated seal includes a plastic layer facing the interior space of the reaction chamber and a conductive layer disposed on the plastic layer; a first heater, the first heater being in contact with or configured to be positioned in contact with the first wall of the reaction chamber to transmit optical signals to the reaction chamber via the contact of the first heater. The reaction chamber is equipped with: a first wall for conductive heat transfer to heat the reaction mixture within the reaction chamber; a second heater that contacts the second wall of the reaction chamber to heat the reaction mixture within the reaction chamber via conductive heat transfer to the reaction chamber via the second wall contacted by the second heater; and an optical waveguide that extends at least partially through the first heater and is configured to transmit optical signals through the first heater and the first wall to the reaction mixture contained within the reaction chamber and / or to transmit optical signals from the reaction mixture contained within the reaction chamber via the first wall and the first heater.
[0242] Implementation Scheme I2. The system according to Implementation Scheme I1, wherein neither the first heater nor the second heater includes a light source.
[0243] Implementation Scheme I3. The system according to Implementation Scheme I1 or I2, wherein each of the first heater and the second heater includes a thermoelectric module.
[0244] Implementation Scheme I4. The system according to any one of Implementation Schemes I1 to I3, wherein the first heater is movable relative to the second heater between a first position and a second position, wherein in the first position the first heater is not in contact with the first wall of the reaction chamber, and in the second position the first heater is in contact with the first wall of the reaction chamber.
[0245] Implementation Scheme I5. The system according to any one of Implementation Schemes I1 to I4, wherein the reaction chamber is part of a box, the box including a box body having a first side, a second side, at least one opening in the box body extending from the first side to the second side, and wherein the first wall includes a first film attached to the first side of the box body and covering a first end of the at least one opening, and wherein a thermally conductive laminated seal is attached to the second side of the box body and covers a second end of the at least one opening, wherein the at least one opening covered by the first film and the thermally conductive laminated seal defines the reaction chamber.
[0246] Implementation Scheme I6. The system according to Implementation Scheme I5, wherein the box body is opaque.
[0247] Implementation Scheme I7. The system according to Implementation Scheme I5 or I6, wherein the first surface is the top surface of the box and the second surface is the bottom surface of the box.
[0248] Implementation Scheme I8. The system according to any one of Implementation Schemes I1 to I7, wherein the plastic layer comprises polypropylene.
[0249] Implementation Scheme I9. The system according to any one of Implementation Schemes I1 to I8, wherein the conductive layer comprises a metal foil.
[0250] Implementation Scheme I10. The system according to Implementation Scheme I9, wherein the metal foil comprises aluminum.
[0251] Implementation Scheme I11. The system according to any one of Implementation Schemes I1 to I10, wherein the conductive layer is reflective and the plastic layer is transparent or translucent.
[0252] Implementation Scheme I12. The system according to any one of Implementation Schemes I1 to I11 further comprises two or more reaction chambers arranged in a group of at least two reaction chambers.
[0253] Implementation Scheme I13. The system according to any one of Implementation Schemes I1 to I12 further includes at least one of an optical transmitter and an optical detector optically coupled to the optical waveguide.
[0254] Implementation Scheme I14. The system according to any one of Implementation Schemes I1 to I13, wherein the optical waveguide comprises an optical fiber.
[0255] Implementation Scheme I15. The system according to any one of Implementation Schemes I1 to I14 further includes a drying agent, said drying agent being adhered to the surface of the plastic layer of the thermally conductive laminated seal facing the interior space of the reaction chamber.
[0256] Implementation Scheme I16. The system according to Implementation Scheme I15, wherein the drying reagent is only adhered to a portion of the outer surface of the plastic layer corresponding to the position of the reaction chamber.
[0257] Implementation Scheme I17. The system according to Implementation Scheme I16, wherein at least a portion of the surface of the plastic layer is treated such that the portion of the surface to which the drying agent adheres has greater hydrophilicity compared to the remaining portion of the surface of the plastic layer.
[0258] Implementation Scheme I18. The system according to Implementation Scheme I16, wherein the portion of the outer surface of the plastic layer to which the drying agent adheres is treated to increase the hydrophilicity of the portion of the outer surface.
[0259] Implementation Scheme I19. The system according to Implementation Scheme I18, wherein the portion of the outer surface of the plastic layer to which the drying agent adheres is treated with corona discharge or plasma treatment to increase the hydrophilicity of the portion of the outer surface.
[0260] Implementation Scheme I20. The system according to any one of Implementation Schemes I5 to I7, wherein the box body is plastic, and the thermally conductive laminate seal is attached to a second side of the box body by heat sealing or ultrasonic welding between the plastic layer and the box body.
[0261] Implementation Scheme I21. The system according to Implementation Scheme I20, wherein the housing body includes one or more energy directors formed on the second surface and at least partially surrounding each of the at least one opening, wherein the energy directors are configured to melt and fuse with the plastic layer during a heat-sealing process or an ultrasonic welding process.
[0262] Implementation Scheme I22. The system according to Implementation Scheme I21, wherein the cartridge body includes: one or more inspection holes formed through the cartridge body at the region to which the thermally conductive laminated seal of the fluid cartridge is attached; and an energy director that at least partially surrounds each inspection hole.
[0263] Implementation Scheme I23. The system according to any one of Implementation Schemes I5 to I7, wherein the thermally conductive laminated seal is attached to the second side of the housing body by an adhesive.
[0264] Implementation Scheme J1. A method for applying thermal energy to a reaction mixture and for transmitting optical signals to and / or from the reaction mixture in a reaction chamber, wherein the reaction mixture is contained within the reaction chamber, the reaction chamber having a transparent or translucent first wall and a second wall including a thermally conductive laminated seal, wherein the thermally conductive laminated seal includes a plastic layer facing the interior space of the reaction chamber and a conductive layer disposed on the plastic layer, the method comprising: contacting the first wall of the reaction chamber with a first heater and heating the reaction mixture within the reaction chamber by conductive thermal energy transfer to the reaction chamber via the first wall contacted by the first heater; contacting the second wall of the reaction chamber with a second heater and heating the reaction mixture within the reaction chamber by conductive thermal energy transfer to the reaction chamber via the second wall contacted by the second heater; and transmitting optical signals through the first heater and the first wall to the reaction mixture contained in the reaction chamber and / or transmitting optical signals from the reaction mixture contained in the reaction chamber through the first wall and the first heater via the optical waveguide extending at least partially through the first heater.
[0265] Implementation Scheme J2. The method according to Implementation Scheme J1, wherein neither the first heater nor the second heater includes a light source.
[0266] Implementation Scheme J3. The method according to Implementation Scheme J1 or J2, wherein each of the first heater and the second heater includes a thermoelectric module.
[0267] Implementation Scheme J4. The method according to any one of Implementation Schemes J1 to J3, further comprising moving the first heater relative to the second heater between a first position and a second position, wherein in the first position the first heater is not in contact with the first wall of the reaction chamber, and in the second position the first heater is in contact with the first wall of the reaction chamber.
[0268] Implementation Scheme J5. The method according to any one of Implementation Schemes J1 to J4, wherein the reaction chamber is part of a box, the box including a box body having a first side, a second side, and at least one opening extending from the first side to the second side, and wherein the first wall includes a first film attached to the first side of the box body and covering a first end of the at least one opening, and wherein a thermally conductive laminated seal is attached to the second side of the box body and covers a second end of the at least one opening, wherein the at least one opening covered by the first film and the thermally conductive laminated seal defines the reaction chamber.
[0269] Implementation Scheme J6. The method according to Implementation Scheme J5, wherein the box body is opaque.
[0270] Implementation Scheme J7. The method according to Implementation Scheme J5 or J6, wherein the first surface is the top surface of the box and the second surface is the bottom surface of the box.
[0271] Implementation Scheme J8. The method according to any one of Implementation Schemes J1 to J7, wherein the plastic layer comprises polypropylene.
[0272] Implementation Scheme J9. The method according to any one of Implementation Schemes J1 to J8, wherein the conductive layer comprises a metal foil.
[0273] Implementation Scheme J10. The method according to Implementation Scheme J9, wherein the metal foil comprises aluminum.
[0274] Implementation Scheme J11. The method according to any one of Implementation Schemes J1 to J10, wherein the conductive layer is reflective and the plastic layer is transparent or translucent.
[0275] Implementation Scheme J12. The method according to any one of Implementation Schemes J1 to J11, further comprising two or more reaction chambers arranged in a group of at least two reaction chambers.
[0276] Implementation J13. The method according to any one of implementations J1 to J12 further includes at least one of an optical transmitter and an optical detector optically coupled to the optical waveguide.
[0277] Implementation Scheme J14. The method according to any one of Implementation Schemes J1 to J13, wherein the optical waveguide comprises an optical fiber.
[0278] Implementation Scheme K1. A valve actuator, the valve actuator being cooperatively arranged relative to one or more fluid flow control valves within a fluid device to selectively actuate each valve to a closed configuration preventing fluid flow or to an open configuration allowing fluid flow, the valve actuator comprising: a valve actuator piston operably engageable with each valve, wherein each valve actuator piston is movable between a first position and a second position, the first position corresponding to one of the closed configuration and the open position of the engaged valve, and the second position corresponding to the other of the open position and the closed position of the engaged valve; a spring coupled to each valve actuator piston for biasing the valve actuator piston to the first position; at least one camshaft supported for rotation about a camshaft rotation axis and including at least one cam cam angle; and an actuator lever, the... An actuator lever is associated with each cam lobe and with each valve actuator piston, wherein the actuator lever includes a pivot connection at which it is mounted for pivoting about a pivot axis; a piston engagement spatially separated from the pivot connection, and wherein the actuator lever is operatively engaged with the associated valve actuator piston at the piston engagement such that pivoting about the pivot axis in a first direction moves the associated valve actuator piston from its first position to its second position; and a cam follower surface disposed between the pivot connection and the piston engagement, wherein the cam follower surface is configured and arranged to engage with an associated cam lobe of the at least one camshaft as the camshaft rotates about the camshaft axis of rotation, thereby causing the actuator lever to pivot in the first direction.
[0279] Implementation Scheme K2. The valve actuator according to Implementation Scheme K1, wherein the valve actuator is arranged cooperatively relative to six fluid flow control valves, and wherein the at least one camshaft comprises three camshafts, and the at least one cam lob of each camshaft comprises two cam lobes.
[0280] Implementation scheme K3. The valve actuator according to implementation scheme K1, wherein the valve actuator is arranged cooperatively relative to eight fluid flow control valves, and wherein the at least one camshaft comprises two camshafts, and the at least one cam lob of each camshaft comprises four cam lobes.
[0281] Implementation scheme K4. The valve actuator according to any one of implementation schemes K1 to K3 further includes a motor coupled to each camshaft for powering rotation of the camshaft about the camshaft rotation axis.
[0282] Implementation scheme K5. The valve actuator according to implementation scheme K4, wherein each motor includes a stepper motor.
[0283] Implementation Scheme K6. A valve actuator according to any one of Implementation Schemes K1 to K5, wherein each valve actuator piston includes: a contact end configured to directly or indirectly contact the associated valve; an extension extending from the contact end and having a width greater than the width of the contact end; and a lever collar having a width smaller than the width of the extension.
[0284] Implementation scheme K7. The valve actuator according to implementation scheme K6, wherein each valve actuator piston further includes a peripheral rib surrounding the contact end.
[0285] Implementation scheme K8. The valve actuator according to implementation scheme K6 or K7, wherein the valve actuator piston further includes a spring housing disposed below the lever collar and defining a hollow cylindrical space in which the spring is seated.
[0286] Implementation Scheme K9. The valve actuator according to Implementation Scheme K8, wherein the width of the spring housing is greater than the width of the lever collar, and wherein the top surface of the spring housing defines an annular lever seat, and wherein the piston engagement of each actuator lever includes a yoke that receives the lever collar and is seated on the lever seat.
[0287] Implementation scheme K10. The valve actuator according to implementation scheme K6 or K7, wherein the valve actuator piston further includes a spring rod below the lever collar, and wherein the spring is coaxially surrounding the spring rod.
[0288] Implementation Scheme K11. The valve actuator according to Implementation Scheme K10, wherein the valve actuator piston further includes an enlarged portion between the lever collar and the spring rod, the enlarged portion having a width greater than the width of the lever collar, wherein the top surface of the enlarged portion defines an annular lever seat, and wherein the piston engagement portion of each actuator lever includes a yoke that receives the lever collar and is seated on the lever seat.
[0289] Implementation Scheme K12. A valve actuator according to any one of embodiments K1 to K11, wherein at least one actuator lever has an "L" shape, the "L" shape including a first leg extending from the pivot connection and a second leg extending laterally from the first leg, wherein an engagement is formed on one side of the second leg between the end of the first leg and the end of the second leg, and wherein a cam follower surface is formed on the first leg between the pivot connection and the second leg.
[0290] Implementation Scheme K13. A valve actuator according to any one of Implementation Schemes K1 to K12, wherein the pivot connection of each actuator lever includes a pivot anchor, the pivot anchor including a partial cylinder and a pivot socket having a shape conforming to the pivot anchor and being configured to rotatably retain the pivot anchor such that the pivot rotation axis corresponds to the longitudinal axis of the partial cylinder.
[0291] Implementation Scheme K14. A valve actuator according to any one of Implementation Schemes K1 to K12, wherein the pivoting connection of each actuator lever includes a pivot rod extending through a pivot hole such that the pivoting rotation axis corresponds to the longitudinal axis of the pivot rod, the pivot hole being formed through the actuator lever.
[0292] Implementation scheme K15. A valve actuator according to any one of implementation schemes K1 to K14, wherein each actuator lever includes a cam ring, and the cam follower surface is formed within the cam ring.
[0293] Implementation Scheme K16. The valve actuator according to Implementation Scheme K13 further includes a frame having an end wall, a bottom wall, a first side wall and a second side wall, wherein the pivot socket is located on the first side wall or the second side wall.
[0294] Implementation Scheme K17. The valve actuator according to Implementation Scheme K14 further includes a frame having an end wall, a bottom wall, a first side wall, a second side wall, and a front wall, wherein the pivot rod extends between the front wall and the end wall.
[0295] Implementation Scheme K18. The valve actuator according to Implementation Scheme K16 or K17 further includes a bearing mount associated with each camshaft and comprising: a mounting block fixed to the bottom wall; an upright support extending from the mounting block; and a bearing disposed within the support at a location spaced apart from the mounting block and configured to rotatably receive the journal end of the associated camshaft.
[0296] Implementation Scheme L1. An actuation mechanism cooperatively arranged relative to a plurality of fluid flow control valves within a fluid device, wherein the plurality of flow control valves are arranged in a circular configuration, and the actuation mechanism is configured to selectively actuate each of the plurality of valves to a closed configuration preventing fluid flow or to an open configuration allowing fluid flow, and wherein the actuation mechanism comprises: a valve actuator piston operably engageable with each of the plurality of valves, wherein each valve actuator piston is axially movable between a first position and a second position, the first position corresponding to one of the closed configuration and the open position of the engaged valve, and the second position corresponding to the other of the open position and the closed position of the engaged valve; and a spring coupled to each valve. An actuator piston for biasing the valve actuator piston to the first position; a cam follower surface associated with each valve actuator piston; and a rotary cam rotatable about a rotation axis corresponding to the center of the circular configuration of the plurality of flow control valves, wherein the rotary cam includes: a cam rod extending radially relative to and rotatable about the rotation axis; and a cam disposed on the radially outer end of the cam rod, wherein the cam rod rotates about the rotation axis to a rotational position of a selected one of the valve actuator pistons such that the cam engages the cam follower surface associated with the selected valve actuator piston, and moves the selected valve actuator piston associated with the cam follower surface engaged by the cam from the first position to the second position.
[0297] Implementation Scheme L2. The actuation mechanism according to Implementation Scheme L1, wherein the first position of the valve actuator piston corresponds to the closed configuration of the associated valve, and the second position of the valve actuator corresponds to the open configuration of the associated valve.
[0298] Implementation scheme L3. The actuation mechanism according to implementation scheme L1 or L2, wherein the cam includes a roller bearing attached to the radially outer end of the cam rod, and wherein the roller bearing is rotatable about a rotation axis corresponding to the longitudinal axis of the cam rod.
[0299] Implementation scheme L4. The actuation mechanism according to any one of implementation schemes L1 to L3 further includes a rotary position sensor configured to detect the rotary position of the rotary cam.
[0300] Implementation scheme L5. The actuation mechanism according to any one of implementation schemes L1 to L4 further includes a cam rotor having a longitudinal axis corresponding to the rotation axis, wherein the cam rod extends radially from the cam rotor.
[0301] Implementation Scheme L6. The actuation mechanism according to Implementation Scheme L5, wherein the cam rotor includes: a central shaft supported for rotation about the rotation axis; a cam rod mounting head including a radially extending flange and an axial wall extending radially from the radially extending flange, wherein the axial wall is radially spaced from the central shaft, and wherein the cam rod is mounted within the cam rod mounting head.
[0302] Implementation Scheme L7. The actuation mechanism according to Implementation Scheme L6, wherein the axial wall of the cam rod mounting head includes a plurality of spaced sensor marks formed around the circumference of the axial wall, and wherein the actuation mechanism further includes an optical sensor, the optical sensor including an optical transmitter on one side of the axial wall and an optical receiver on the opposite side of the axial wall.
[0303] Implementation scheme L8. The actuation mechanism according to any one of implementation schemes L5 to L7 further includes a cam drive, the cam drive including a motor and one or more gears connecting the motor to the cam rotor.
[0304] Implementation Scheme L9. An actuation mechanism according to any one of Implementation Schemes L1 to L8, wherein each valve actuator piston includes: a contact rod configured to directly or indirectly contact the engaged valve; a cam block having a cam follower surface disposed on the cam block; a lower rod projecting below the cam block; and a spring rod projecting below the lower rod, wherein the spring is coaxially disposed on the spring rod.
[0305] Implementation scheme L10. The actuation mechanism according to implementation scheme L9 further includes a stop flange at the base of the contact rod to prevent over-insertion of the contact rod.
[0306] Implementation scheme L11. The actuation mechanism according to implementation scheme L9 or L10, wherein the radially inner side of the cam block is narrower than the radially outer side of the cam block in the circumferential direction.
[0307] Implementation scheme L12. The actuation mechanism according to any one of implementation schemes L1 to L11, wherein the surface of the cam follower has an inverted V shape.
[0308] Implementation scheme L13. The actuation mechanism according to implementation scheme L12, wherein the cam follower surface has a flat surface at the apex of the inverted V-shape.
[0309] Implementation Scheme M1. A system for performing one or more processes within a fluid cartridge, wherein the fluid cartridge includes: a plurality of fluid chambers; a fluid passage connecting each of the fluid chambers to at least one other fluid chamber; and a plurality of valves selectively configured to allow fluid flow through or through an open state or to prevent fluid flow through or through a closed state, and wherein the system includes: a pump mechanism operably engaged with the fluid cartridge for moving fluid between the chambers and through the plurality of passages; a plurality of valve actuator pistons, wherein each valve actuator piston is movable between a first position and a second position and operably associated with one of the plurality of valves of the fluid cartridge, and wherein, when the valve actuator piston is in its first position, the valve actuator piston applies a force to the operably associated valve to place the valve in one of the closed state and the open state, and when the valve is actuated... When the valve actuator piston is in its second position, the force applied by the valve actuator piston is removed from the operatively associated valve to allow the valve to be in the other of the closed and open states; a biasing element associated with each valve actuator piston for applying a biasing force to the associated valve actuator piston to cause the associated valve actuator piston to enter its first position; and one or more piston actuator mechanisms coupled to or otherwise selectively engageable with each valve actuator piston, and configured and arranged to selectively apply a force to at least one valve actuator piston coupled to or engaged by the piston actuator mechanism to move the valve actuator piston from its first position to its second position against the biasing force, and selectively remove the force applied to the valve actuator piston to allow the valve actuator piston to move back from its second position to its first position under the biasing force.
[0310] Implementation scheme M2. The system according to implementation scheme M1, wherein the first position of each valve actuator piston corresponds to the closed state of the associated valve, and the second position of each valve actuator corresponds to the open state of the associated valve.
[0311] Implementation Scheme M3. The system according to Implementation Scheme M1 or M2, wherein the fluid cartridge includes a syringe barrel and a syringe stop disposed within the syringe barrel, wherein the fluid passage includes a fluid passage network that directly or indirectly connects one or more of the plurality of fluid chambers to the syringe barrel, and wherein the pump mechanism includes: a movable syringe plunger configured to engage with the syringe stop to removably connect the syringe stop to the syringe plunger; and a syringe driver including a motor coupled to the syringe plunger and configured to actuate the syringe plunger to move the syringe stop within the syringe barrel, thereby moving the engaged syringe stop within the syringe barrel to draw fluid into or discharge fluid from the syringe barrel.
[0312] Implementation Scheme M4. A system according to any one of Implementation Schemes M1 to M3, wherein the system comprises: a support bracket on which the fluid cartridge is operatively supported; and a plurality of actuator heads disposed within the support bracket, each actuator head being associated with one of the valves of the fluid cartridge and one of the valve actuator pistons, wherein each actuator head is configured to be movable relative to the support bracket in response to movement of the associated valve actuator piston between a first position and a second position to engage the associated valve to open or close the associated valve.
[0313] Implementation Scheme M5. A system according to any one of embodiments M1 to M4, wherein at least a portion of the plurality of valves is arranged in a circular configuration such that the valve actuator piston associated with the portion of the plurality of valves is also arranged in a circular configuration, wherein each of the circularly arranged valve actuator pistons includes a cam follower surface, and wherein the one or more piston actuator mechanisms include a rotary piston actuator comprising: a rotary cam rotatable about a rotation axis corresponding to the center of the circular configuration of the valves, wherein the rotary cam includes: a cam rod extending radially relative to and rotatable about the rotation axis; and a cam, wherein... A cam rod is arranged on the radially outer end of the cam rod, wherein the rotary piston actuator is configured to position the cam rod in a rotational position relative to the axis of rotation to engage the cam follower surface associated with a selected one of the circularly arranged valve actuator pistons, such that the valve actuator piston associated with the cam follower surface engaged by the cam moves from a first position to a second position and then moves the cam rod away from the rotational position of the selected valve actuator piston to disengage from the cam follower surface associated with the selected valve actuator piston and allow the selected valve actuator piston to move from the second position to the first position.
[0314] Implementation Scheme M6. The system according to Implementation Scheme M5, wherein the cam of the rotary piston actuator includes a roller bearing attached to the radially outer end of the cam rod, and wherein the roller bearing is rotatable about a rotation axis corresponding to the longitudinal axis of the cam rod.
[0315] Implementation scheme M7. The system according to implementation scheme M5 or M6, wherein the rotary piston actuator further includes a rotary position sensor configured to detect the rotational position of the rotary cam.
[0316] Implementation scheme M8. The system according to any one of implementation schemes M5 to M7, wherein the rotary piston actuator further includes a cam rotor having a longitudinal axis corresponding to the rotation axis, wherein the cam rod extends radially from the cam rotor.
[0317] Implementation Scheme M9. The system according to Implementation Scheme M8, wherein the cam rotor of the rotary piston actuator includes: a central shaft supported for rotation about the rotation axis; and a cam rod mounting head including a radially extending flange and an axial wall extending from the radially extending flange, wherein the axial wall is radially spaced from the central shaft, and wherein the cam rod is mounted within the cam rod mounting head.
[0318] Implementation Scheme M10. The system according to Implementation Scheme M9, wherein the axial wall of the cam rod mounting head includes a plurality of spaced-apart sensor marks formed around the circumference of the axial wall, and wherein the rotary piston actuator further includes an optical sensor comprising an optical transmitter on one side of the axial wall and an optical receiver on the opposite side of the axial wall.
[0319] Implementation scheme M11. The system according to any one of implementation schemes M8 to M10, wherein the rotary piston actuator further includes a cam drive, the cam drive including a motor and one or more gears connecting the motor to the cam rotor.
[0320] Implementation Scheme M12. The system according to any one of embodiments M5 to M11, wherein each of the valve actuator pistons arranged in the circular configuration includes: a contact rod configured to directly or indirectly contact the engaged valve; a cam block having a cam follower surface disposed on the cam block; a lower rod projecting below the cam block; and a spring rod projecting below the lower rod, wherein the biasing element comprises a spring coaxially disposed on the spring rod.
[0321] Implementation scheme M13. The system according to implementation scheme M12, wherein the radially inner side of the cam block is narrower than the radially outer side of the cam block in the circumferential direction relative to the axis of rotation.
[0322] Implementation Scheme M14. A system according to any one of embodiments M1 to M13, wherein the one or more piston actuator mechanisms include a cam-driven piston actuator comprising: at least one camshaft supported for rotation about a camshaft rotation axis and including at least one cam lob; and an actuator lever associated with each cam lob and with at least a portion of each of the plurality of valve actuator pistons, wherein each actuator lever includes: a pivoting connection at which the actuator lever is mounted for pivoting movement about a pivot rotation axis; and a piston engagement portion for engaging the piston. The actuator lever is spatially separated from the pivot connection and at the piston engagement, the actuator lever is operatively engaged with the associated valve actuator piston such that pivoting movement of the actuator lever about the pivot rotation axis in a first direction moves the associated valve actuator piston from its first position to its second position; and a cam follower surface is disposed between the pivot connection and the piston engagement, wherein the cam follower surface is configured and arranged to engage by an associated cam lobe of the at least one camshaft when the camshaft rotates about the camshaft rotation axis, so as to pivot the actuator lever in the first direction.
[0323] Implementation scheme M15. The system according to implementation scheme M14 further includes six valve actuator pistons arranged cooperatively relative to the six valves, and wherein at least one camshaft of the cam-driven piston actuator includes three camshafts, and the at least one cam lob of each camshaft includes two cam lobes.
[0324] Implementation scheme M16. The system according to implementation scheme M14 further includes eight valve actuator pistons arranged cooperatively relative to eight valves, and wherein at least one camshaft of the cam-driven piston actuator includes two camshafts, and the at least one cam lob of each camshaft includes four cam lobes.
[0325] Implementation scheme M17. The system according to any one of implementation schemes M14 to M16, wherein the cam-driven piston actuator further includes a motor coupled to each camshaft for powering rotation of the camshaft about the camshaft rotation axis.
[0326] Implementation Scheme M18. The system according to any one of Implementation Schemes M14 to M17, wherein each valve actuator piston associated with the actuator lever includes: a contact end configured to directly or indirectly contact the associated valve; an extension extending from the contact end and having a width greater than the width of the contact end; and a lever collar having a width smaller than the width of the extension.
[0327] Implementation scheme M19. The system according to implementation scheme M18, wherein each valve actuator piston associated with the actuator lever further includes a spring housing disposed below the lever collar and defining a hollow cylindrical space, and wherein the biasing element includes a spring seated within the space.
[0328] Implementation scheme M20. The system according to implementation scheme M19, wherein the width of the spring housing is greater than the width of the lever collar, wherein the top surface of the spring housing defines an annular lever seat, and wherein the piston engagement of each actuator lever includes a yoke that receives the lever collar and is seated on the lever seat.
[0329] Implementation Scheme M21. The system according to Implementation Scheme M18, wherein each valve actuator piston associated with the actuator lever further includes: a spring rod extending below the lever collar, wherein the biasing element includes a spring coaxially surrounding the spring rod; and an enlargement portion between the lever collar and the spring rod, having a width greater than the width of the lever collar, wherein the top surface of the enlargement portion defines an annular lever seat, and wherein the piston engagement portion of each actuator lever includes a yoke receiving the lever collar and sitting on the lever seat.
[0330] Implementation Scheme M22. The system according to any one of Implementation Schemes M14 to M21, wherein the pivot connection of each actuator lever of the cam-driven piston actuator includes a pivot anchor, the pivot anchor including a partial cylinder and a pivot socket having a shape conforming to the pivot anchor and being configured to rotatably retain the pivot anchor such that the pivot rotation axis corresponds to the longitudinal axis of the partial cylinder.
[0331] Implementation scheme M23. The system according to any one of implementation schemes M14 to M21, wherein the pivot connection of each actuator lever of the cam-driven piston actuator includes a pivot rod extending through a pivot hole such that the pivot rotation axis corresponds to the longitudinal axis of the pivot rod, the pivot hole being formed through the actuator lever.
[0332] Implementation scheme M24. The system according to any one of implementation schemes M14 to M23, wherein each actuator lever of the cam-driven piston actuator includes a cam ring, and the cam follower surface is formed within the cam ring.
[0333] Implementation scheme M25. The system according to implementation scheme M22, wherein the cam-driven piston actuator includes a frame having an end wall, a bottom wall, a first side wall and a second side wall, and wherein the pivot socket is located on the first side wall or the second side wall.
[0334] Implementation Scheme M26. The system according to Implementation Scheme M23, wherein the cam-driven piston actuator includes a frame having an end wall, a bottom wall, a first side wall, a second side wall and a front wall, and wherein the pivot rod extends between the front wall and the end wall.
[0335] Implementation Scheme M27. A system according to any one of embodiments M1 to M26, wherein the plurality of chambers of the fluid cartridge includes at least one reaction chamber, and wherein the system further includes: a first heater and a second heater arranged in an opposing, spaced-apart configuration to receive the at least one reaction chamber between the first heater and the second heater; an actuator for moving the first heater relative to the second heater to clamp the at least one reaction chamber between the first heater and the second heater by moving the first heater toward the second heater and / or by moving the second heater toward the first heater when the at least one reaction chamber is arranged between the first heater and the second heater, wherein the first heater and the second heater are configured to apply thermal energy to or absorb thermal energy from the at least one reaction chamber clamped between the first heater and the second heater; and an optical fiber aligned with or at least partially extending through an opening extending through the first heater, and configured to transmit optical signals through the first heater to and / or from the at least one reaction chamber.
[0336] Implementation Scheme M28. The system according to Implementation Scheme M27, wherein each of the first heater and the second heater includes at least one thermal element, the at least one thermal element being configured to emit thermal energy to heat a body in thermal contact with the thermal element and / or absorb thermal energy to cool a body in thermal contact with the thermal element, and wherein the optical fiber extends at least partially through an aperture formed by each thermal element of the first heater, each optical fiber being configured to transmit an optical signal to and / or from a different one of the at least one reaction chamber.
[0337] Implementation scheme M29. The system according to implementation scheme M28, wherein each of the first heater and the second heater includes a thermal block associated with each thermal element, wherein each thermal block has an exposed contact surface that contacts one of the at least one reaction chamber.
[0338] Implementation scheme M30. The system according to implementation scheme M28 or M29, wherein each of the first heater and the second heater includes a heat sink, wherein the thermal element of each of the first heater and the second heater is in thermal contact with the heat sink, and wherein the heat sink of at least one of the first heater and the second heater includes a heat sink fin.
[0339] Implementation scheme M31. The system according to any one of implementation schemes M27 to M30 further includes at least one of an optical transmitter and an optical detector optically coupled to the optical fiber.
[0340] Implementation Scheme M32. The system according to any one of Implementation Schemes M27 to M31 further includes a movable tray for supporting the fluid cartridge and configured to move the fluid cartridge supported by the tray between a first position and a second position, wherein in the first position the at least one reaction chamber is not arranged between the first heater and the second heater, and in the second position the at least one reaction chamber is arranged between the first heater and the second heater.
[0341] Implementation Scheme N1. A method of manufacturing a fluid cartridge, the method comprising: attaching a first film to a cartridge body, wherein the cartridge body has a first side, a second side, and at least one opening extending from the first side to the second side, wherein the first film is secured to at least a portion of the first side to cover a first end of the at least one opening; and attaching a thermally conductive laminated seal to a portion of a second side of the cartridge body to cover a second end of the at least one opening, wherein the thermally conductive laminated seal comprises a plastic layer facing the at least one opening and a conductive layer disposed on the plastic layer.
[0342] Implementation Scheme N2. The method according to Implementation Scheme N1, wherein the box body is opaque.
[0343] Implementation scheme N3. The method according to implementation scheme N1 or N2, wherein at least a portion of the first film covering the at least one opening is transparent or translucent.
[0344] Implementation scheme N4. The method according to any one of implementation schemes N1 to N3, wherein the plastic layer of the thermally conductive laminated seal comprises polypropylene.
[0345] Implementation scheme N5. The method according to any one of implementation schemes N1 to N4, wherein the conductive layer of the thermally conductive laminated seal comprises a metal foil.
[0346] Implementation Scheme N6. The method according to Implementation Scheme N5, wherein the metal foil comprises aluminum.
[0347] Implementation Scheme N7. The method according to any one of Implementation Schemes N1 to N6, wherein the conductive layer of the thermally conductive laminated seal is reflective, and the plastic layer of the thermally conductive laminated seal is transparent or translucent.
[0348] Implementation scheme N8. The method according to any one of implementation schemes N1 to N7, wherein the at least one opening in the box body comprises two or more openings arranged as a group of at least two openings.
[0349] Implementation scheme N9. The method according to any one of embodiments N1 to N8 further includes, before or after attaching the thermally conductive laminated seal to a portion of the second side of the box body, adhering a desiccant to at least a portion of the surface of the plastic layer of the thermally conductive laminated seal facing the at least one opening.
[0350] Implementation Scheme N10. The method according to Implementation Scheme N9, wherein the reagent comprises components for performing polymerase chain reaction (PCR).
[0351] Implementation scheme N11. The method according to implementation scheme N9 or N10, further comprising adhering the drying agent to only the portion of the surface of the plastic layer corresponding to the location of the at least one opening.
[0352] Implementation scheme N12. The method according to implementation scheme N11, wherein the edge of the drying agent is spaced apart from the edge of the at least one opening.
[0353] Implementation Scheme N13. The method according to Implementation Scheme N11 or N12, wherein the portion of the surface to which the drying agent is adhered to corresponds only to the location of the at least one opening comprises treating at least a portion of the surface of the plastic layer such that the portion of the surface to which the drying agent is adhered has greater hydrophilicity compared to the remaining portion of the surface of the plastic layer.
[0354] Implementation Scheme N14. The method according to Implementation Scheme N13 further includes treating the portion of the surface of the plastic layer to which the drying agent adheres, so as to increase the hydrophilicity of the treated portion of the surface of the plastic layer compared with the untreated portion of the surface of the plastic layer.
[0355] Implementation Scheme N15. The method according to Implementation Scheme N14, wherein the untreated portion of the surface of the plastic layer is hydrophobic.
[0356] Implementation Scheme N16. The method according to Implementation Scheme N14 or N15 further includes treating the portion of the surface of the plastic layer to which the drying agent adheres with corona discharge or plasma to increase the hydrophilicity of the treated portion of the surface of the plastic layer compared to the untreated portion of the surface of the plastic layer.
[0357] Implementation Scheme N17. The method according to Implementation Scheme N16, wherein treating the surface of the plastic layer with corona discharge or plasma to the portion to which the drying agent adheres comprises: attaching a mask to the surface of the plastic layer, wherein the mask has one or more openings exposing a portion of the surface of the plastic layer; and applying corona discharge or plasma to the masked surface of the plastic layer, wherein the portion of the surface of the plastic layer exposed only through the one or more openings in the mask is treated by corona discharge or plasma treatment.
[0358] Implementation scheme N18. The method according to any one of implementation schemes N1 to N4, wherein the box body and the first film each comprise plastic, and wherein the first film is fixed to a first side of the box body by thermal welding, adhesive, or chemical bonding.
[0359] Implementation Scheme N19. The method according to Implementation Scheme N18, wherein the box body and the first film each comprise polypropylene, and wherein the first film has a thickness of about 0.1 mm.
[0360] Implementation scheme N20. The method according to any one of implementation schemes N1 to N17, wherein the box body comprises plastic, and wherein the thermally conductive laminated seal is attached to a second side of the box body by heat-sealing or ultrasonically welding the plastic layer of the thermally conductive laminated seal to the box body.
[0361] Implementation Scheme N21. The method according to Implementation Scheme N20, wherein the housing body includes one or more energy directors formed on the second surface and at least partially surrounding each of the at least one opening, and wherein heat-sealing or ultrasonically welding the plastic layer of the thermally conductive laminate seal to the housing body includes melting the energy director and melting the molten energy director with the plastic layer.
[0362] Implementation Scheme N22. The method according to Implementation Scheme N21, wherein the housing body includes: one or more inspection holes formed through the housing body at the region to which the thermally conductive laminated seal of the housing body is attached; and an energy director at least partially surrounding each inspection hole, and wherein the method includes the step of inspecting each of the one or more inspection holes after heat-sealing or ultrasonically welding a plastic layer of the thermally conductive laminated seal to the housing body to determine whether the energy director at least partially surrounding the inspection hole has melted and at least partially blocked the inspection hole.
[0363] Implementation scheme N23. The method according to implementation scheme N22, wherein the energy director at least partially surrounding each of the at least one opening and the energy director at least partially surrounding each inspection hole have the same size.
[0364] Implementation scheme N24. The method according to implementation scheme N22, wherein the energy director at least partially surrounding each of the at least one opening and the energy director at least partially surrounding each inspection hole have different sizes.
[0365] Implementation scheme N25. The method according to any one of implementation schemes N21 to N24, wherein each energy director includes an elevated rib, and wherein the rib has a triangular cross-sectional shape forming the pointed edge of the rib.
[0366] Implementation scheme N26. The method according to any one of implementation schemes N22 to N25, wherein the energy director surrounding at least part of each inspection hole is configured to completely block the inspection hole after the step of attaching the thermally conductive laminated seal to a portion of the second side of the housing body.
[0367] Implementation scheme N27. The method according to any one of implementation schemes N20 to N26, wherein the first film comprises plastic, and wherein the first film is fixed to a first side of the box body by thermal welding, adhesive or chemical bonding.
[0368] Implementation Scheme N28. The method according to Implementation Scheme N27, wherein the box body and the first film each comprise polypropylene, and wherein the first film has a thickness of about 0.1 mm.
[0369] Implementation scheme N29. The method according to any one of implementation schemes N1 to N19, wherein the thermally conductive laminated seal is attached to the second side of the box body by means of an adhesive.
[0370] Implementation scheme N30. The method according to any one of implementation schemes N1 to N29 further includes attaching a second film to at least a portion of the second surface of the housing body that is not covered by the thermally conductive laminated seal, and covering one or more grooves formed in the second surface of the housing body to form one or more channels traversing a portion of the second surface.
[0371] Implementation scheme N31. The method according to any one of implementation schemes N1 to N30, wherein the first film attached to a first surface of the box body covers one or more grooves formed in the first surface to form one or more channels traversing a portion of the first surface.
[0372] Implementation Scheme N32. The method according to Implementation Scheme N31, wherein the second film includes a cut that exposes the at least one opening, and wherein the thermally conductive laminated seal is attached to a second side of the box body within the cut of the second film.
[0373] Implementation scheme N33. The method according to any one of implementation schemes N1 to N32, wherein the box body includes one or more pools directly or indirectly connected to the at least one opening, wherein the method further includes attaching a cover to the box body over one or more of the pools to form a partially enclosed chamber having each covered pool.
[0374] Implementation Scheme N34. The method according to Implementation Scheme N33, wherein the cover attached to the box body over the one or more pools includes a protective vent hood, the protective vent hood comprising: a vent membrane configured to contain liquid in the one or more pools and having through-holes formed therein to allow vapor to pass through the vent membrane; and a protective cover fixed to the vent membrane to block the through-holes and reduce or prevent vapor passage, wherein the protective cover can be peeled off from the vent membrane by a user before using the box.
[0375] Implementation scheme N35. The method according to implementation scheme N34, wherein the venting membrane of the venting hood includes blind tube holes that partially extend through the thickness of the venting membrane.
[0376] Implementation Scheme O1. A method of manufacturing a fluid cartridge, the method comprising: attaching a first film to a cartridge body, wherein the cartridge body has a first side, a second side, and at least one opening extending from the first side to the second side, wherein the first film is secured to at least a portion of the first side to cover a first end of the at least one opening; attaching a seal to at least a portion of a second side of the cartridge body to cover a second end of the at least one opening, wherein the seal includes a plastic layer facing the at least one opening; and adhering a desiccant to at least a portion of the surface of the plastic layer of the seal facing the at least one opening before or after attaching the seal to a portion of the second side of the cartridge body.
[0377] Implementation scheme O2. The method according to implementation scheme O1, wherein the box body is opaque.
[0378] Implementation scheme O3. The method according to implementation scheme O1 or O2, wherein at least a portion of the first film covering the at least one opening is transparent or translucent.
[0379] Implementation scheme O4. The method according to any one of implementation schemes O1 to O3, wherein the plastic layer of the seal comprises polypropylene.
[0380] Implementation scheme O5. The method according to any one of implementation schemes O1 to O4, wherein the at least one opening in the box body comprises two or more openings arranged as a group of at least two openings.
[0381] Implementation Scheme O6. The method according to any one of Implementation Schemes O1 to O5, wherein the reagent comprises components for performing polymerase chain reaction (PCR).
[0382] Implementation scheme O7. The method according to any one of implementation schemes O1 to O6, further comprising adhering the drying agent to only a portion of the surface of the plastic layer corresponding to the location of the at least one opening.
[0383] Implementation scheme O8. The method according to implementation scheme O7, wherein the edge of the drying agent is spaced apart from the edge of the at least one opening.
[0384] Implementation scheme O9. The method according to implementation scheme O7 or O8, wherein the portion of the surface to which the drying agent is adhered to corresponds only to the location of the at least one opening comprises treating at least a portion of the surface of the plastic layer such that the portion of the surface to which the drying agent is adhered has greater hydrophilicity compared to the remaining portion of the surface of the plastic layer.
[0385] Implementation Scheme O10. The method according to Implementation Scheme O9 further includes treating the portion of the surface of the plastic layer to which the drying agent adheres, so as to increase the hydrophilicity of the treated portion of the surface of the plastic layer compared with the untreated portion of the surface of the plastic layer.
[0386] Implementation Scheme O11. The method according to Implementation Scheme O10, wherein the untreated portion of the surface of the plastic layer is hydrophobic.
[0387] Implementation Scheme O12. The method according to Implementation Scheme O10 or O11 further includes treating the portion of the surface of the plastic layer to which the drying agent adheres with corona discharge or plasma to increase the hydrophilicity of the treated portion of the surface of the plastic layer compared to the untreated portion of the surface of the plastic layer.
[0388] Implementation Scheme O13. The method according to Implementation Scheme O12, wherein treating the surface of the plastic layer with corona discharge or plasma to the portion to which the drying agent adheres comprises: attaching a mask to the surface of the plastic layer, wherein the mask has one or more openings exposing a portion of the surface of the plastic layer; and applying corona discharge or plasma to the masked surface of the plastic layer, wherein the portion of the surface of the plastic layer exposed only through the one or more openings in the mask is treated by corona discharge or plasma treatment.
[0389] Implementation scheme O14. The method according to any one of implementation schemes O1 to O4, wherein the box body and the first film each comprise plastic, and wherein the first film is fixed to a first side of the box body by thermal welding, adhesive, or chemical bonding.
[0390] Implementation Scheme O15. The method according to Implementation Scheme O14, wherein the box body and the first film each comprise polypropylene, and wherein the first film has a thickness of about 0.1 mm.
[0391] Implementation scheme O16. The method according to any one of embodiments O1 to O13, wherein the box body comprises plastic, and wherein the seal is attached to a second side of the box body by heat-sealing or ultrasonically welding the plastic layer of the seal to the box body.
[0392] Implementation Scheme O17. The method according to Implementation Scheme O16, wherein the housing body includes one or more energy directors formed on the second surface and at least partially surrounding each of the at least one opening, and wherein heat-sealing or ultrasonically welding the plastic layer of the seal to the housing body includes melting the energy director and melting the molten energy director with the plastic layer.
[0393] Implementation Scheme O18. The method according to Implementation Scheme O17, wherein the housing body includes: one or more inspection holes formed through the housing body at the area to which the seal of the housing body is attached; and an energy director at least partially surrounding each inspection hole, and wherein the method includes the step of inspecting each of the one or more inspection holes after heat-sealing or ultrasonically welding a plastic layer of the seal to the housing body to determine whether the energy director at least partially surrounding the inspection hole has melted and at least partially blocked the inspection hole.
[0394] Implementation scheme O19. The method according to implementation scheme O18, wherein the energy director at least partially surrounding each of the at least one opening and the energy director at least partially surrounding each inspection hole have the same size.
[0395] Implementation scheme O20. The method according to implementation scheme O18, wherein the energy director at least partially surrounding each of the at least one opening and the energy director at least partially surrounding each inspection hole have different sizes.
[0396] Implementation scheme O21. The method according to any one of implementation schemes O17 to O20, wherein each energy director includes an elevated rib, and wherein the rib has a triangular cross-sectional shape forming the pointed edge of the rib.
[0397] Implementation scheme O22. The method according to any one of implementation schemes O18 to O21, wherein the energy guide surrounding at least partially each inspection hole is configured to completely block the inspection hole after the step of attaching the seal to a portion of the second side of the housing body.
[0398] Implementation scheme O23. The method according to any one of implementation schemes O16 to O22, wherein the first film comprises plastic, and wherein the first film is fixed to a first side of the box body by thermal welding, adhesive or chemical bonding.
[0399] Implementation scheme O24. The method according to implementation scheme O23, wherein the box body and the first film each comprise polypropylene, and wherein the first film has a thickness of about 0.1 mm.
[0400] Implementation scheme O25. The method according to any one of implementation schemes O1 to O15, wherein the seal is attached to the second side of the box body by means of an adhesive.
[0401] Implementation scheme O26. The method according to any one of embodiments O1 to O25 further includes attaching a second film to at least a portion of the second surface of the box body that is not covered by the seal, and covering one or more grooves formed in the second surface of the box body to form one or more channels traversing a portion of the second surface.
[0402] Implementation scheme O27. The method according to implementation scheme O26, wherein the second film includes a cut that exposes the at least one opening, and wherein the seal is attached to a second side of the box body within the cut of the second film.
[0403] Implementation scheme O28. The method according to any one of implementation schemes O1 to O25, wherein the seal includes a second film that, in addition to covering the second end of the at least one opening, also covers one or more grooves formed in the second surface of the box body to form one or more channels traversing a portion of the second surface.
[0404] Implementation scheme O29. The method according to any one of implementation schemes O1 to O28, wherein the first film attached to a first surface of the box body covers one or more grooves formed in the first surface to form one or more channels traversing a portion of the first surface.
[0405] Implementation scheme O30. The method according to any one of implementation schemes O1 to O29, wherein the box body includes one or more pools directly or indirectly connected to the at least one opening, wherein the method further includes attaching a cover to the box body over one or more of the pools to form at least a partially enclosed chamber having each covered pool.
[0406] Implementation Scheme O31. The method according to Implementation Scheme O30, wherein the cover attached to the box body over the one or more pools includes a protective vent hood, the protective vent hood comprising: a vent membrane configured to contain liquid in the one or more pools and having through-holes formed therein to allow vapor to pass through the vent membrane; and a protective cover fixed to the vent membrane to block the through-holes and reduce or prevent vapor passage, wherein the protective cover can be peeled off from the vent membrane by a user before using the box.
[0407] Implementation scheme O32. The method according to implementation scheme O31, wherein the venting membrane of the venting hood includes blind tube holes that partially extend through the thickness of the venting membrane.
[0408] Implementation Scheme P1. A method of manufacturing a fluid cartridge, the method comprising: attaching a first film to a cartridge body, wherein the cartridge body comprises plastic and has a first side, a second side, and at least one opening in the cartridge body extending from the first side to the second side, wherein the first film is secured to at least a portion of the first side to cover a first end of the at least one opening; and attaching a seal to at least a portion of a second side of the cartridge body to cover a second end of the at least one opening, wherein the cartridge body includes one or more energy directors formed on the second side and at least partially surrounding each of the at least one opening, wherein the seal includes a plastic layer facing the at least one opening, and wherein attaching the seal to the second side of the cartridge body comprises heat-sealing or ultrasonically welding the plastic layer of the seal to the cartridge body by melting the energy director and melting the molten energy director with the plastic layer.
[0409] Implementation scheme P2. The method according to implementation scheme P1, wherein the box body is opaque.
[0410] Implementation scheme P3. The method according to implementation scheme P1 or P2, wherein at least a portion of the first film covering the at least one opening is transparent or translucent.
[0411] Implementation scheme P4. The method according to any one of implementation schemes P1 to P3, wherein the plastic layer of the seal comprises polypropylene.
[0412] Implementation scheme P5. The method according to any one of implementation schemes P1 to P4, wherein the plastic layer of the seal is transparent or translucent.
[0413] Implementation scheme P6. The method according to any one of implementation schemes P1 to P5, wherein the at least one opening in the box body comprises two or more openings arranged as a group of at least two openings.
[0414] Implementation scheme P7. The method according to any one of implementation schemes P1 to P6 further includes, before or after attaching the seal to a portion of a second side of the box body, adhering a desiccant to at least a portion of the surface of the plastic layer of the seal facing the at least one opening.
[0415] Implementation Scheme P8. The method according to Implementation Scheme P7, wherein the reagent contains components for performing polymerase chain reaction (PCR).
[0416] Implementation scheme P9. The method according to implementation scheme P7 or P8 further includes adhering the drying agent to the surface of the plastic layer only to the portion corresponding to the location of the at least one opening.
[0417] Implementation scheme P10. The method according to implementation scheme P9, wherein the edge of the drying agent is spaced apart from the edge of the at least one opening.
[0418] Implementation scheme P11. The method according to implementation scheme P9 or P10, wherein the portion of the surface to which the drying agent is adhered to corresponds only to the location of the at least one opening comprises treating at least a portion of the surface of the plastic layer such that the portion of the surface to which the drying agent is adhered has greater hydrophilicity than the remaining portion of the surface of the plastic layer.
[0419] Implementation Scheme P12. The method according to Implementation Scheme P11 further includes treating the portion of the surface of the plastic layer to which the drying agent adheres, so as to increase the hydrophilicity of the treated portion of the surface of the plastic layer compared with the untreated portion of the surface of the plastic layer.
[0420] Implementation scheme P13. The method according to implementation scheme P12, wherein the untreated portion of the surface of the plastic layer is hydrophobic.
[0421] Implementation Scheme P14. The method according to Implementation Scheme P12 or P13 further includes treating the portion of the surface of the plastic layer to which the drying agent adheres with corona discharge or plasma to increase the hydrophilicity of the treated portion of the surface of the plastic layer compared to the untreated portion of the surface of the plastic layer.
[0422] Implementation Scheme P15. The method according to Implementation Scheme P14, wherein treating the surface of the plastic layer with corona discharge or plasma to the portion to which the drying agent adheres comprises: attaching a mask to the surface of the plastic layer, wherein the mask has one or more openings exposing a portion of the surface of the plastic layer; and applying corona discharge or plasma to the masked surface of the plastic layer, wherein the portion of the surface of the plastic layer exposed only through the one or more openings in the mask is treated by corona discharge or plasma treatment.
[0423] Implementation scheme P16. The method according to any one of implementation schemes P1 to P4, wherein the first film comprises plastic, and wherein the first film is fixed to a first side of the box body by thermal welding, adhesive or chemical bonding.
[0424] Implementation Scheme P17. The method according to Implementation Scheme P16, wherein the box body and the first film each comprise polypropylene, and wherein the first film has a thickness of about 0.1 mm.
[0425] Implementation Scheme P18. The method according to any one of Implementation Schemes P1 to P17, wherein the housing body comprises: one or more inspection holes formed through the housing body at the area to which the seal of the housing body is attached; and an energy director at least partially surrounding each inspection hole, and wherein the method includes the step of inspecting each of the one or more inspection holes after heat-sealing or ultrasonically welding a plastic layer of the seal to the housing body to determine whether the energy director at least partially surrounding the inspection hole has melted and at least partially blocked the inspection hole.
[0426] Implementation scheme P19. The method according to implementation scheme P18, wherein the energy director at least partially surrounding each of the at least one opening and the energy director at least partially surrounding each inspection hole have the same size.
[0427] Implementation scheme P20. The method according to implementation scheme P18, wherein the energy director at least partially surrounding each of the at least one opening and the energy director at least partially surrounding each inspection hole have different sizes.
[0428] Implementation scheme P21. The method according to any one of implementation schemes P17 to P20, wherein each energy director includes an elevated rib, and wherein the rib has a triangular cross-sectional shape forming the pointed edge of the rib.
[0429] Implementation scheme P22. The method according to any one of implementation schemes P18 to P21, wherein the energy guide surrounding at least partially each inspection hole is configured to completely block the inspection hole after the step of attaching the seal to a portion of the second side of the housing body.
[0430] Implementation scheme P23. The method according to any one of implementation schemes P18 to P22, wherein the first film comprises plastic, and wherein the first film is fixed to a first side of the box body by thermal welding, adhesive or chemical bonding.
[0431] Implementation Scheme P24. The method according to Implementation Scheme P23, wherein the box body and the first film each comprise polypropylene, and wherein the first film has a thickness of about 0.1 mm.
[0432] Implementation scheme P25. The method according to any one of implementation schemes P1 to P24 further includes attaching a second film to at least a portion of the second surface of the box body that is not covered by the seal, and covering one or more grooves formed in the second surface of the box body to form one or more channels traversing a portion of the second surface.
[0433] Implementation Scheme P26. The method according to Implementation Scheme P25, wherein the second film includes a cut that exposes the at least one opening, and wherein the seal is attached to a second side of the box body within the cut of the second film.
[0434] Implementation scheme P27. The method according to any one of implementation schemes P1 to P24, wherein the seal includes a second film that, in addition to covering the second end of the at least one opening, also covers one or more grooves formed in the second surface of the box body to form one or more channels traversing a portion of the second surface.
[0435] Implementation scheme P28. The method according to any one of implementation schemes P1 to P27, wherein the first film attached to a first surface of the box body covers one or more grooves formed in the first surface to form one or more channels traversing a portion of the first surface.
[0436] Implementation scheme P29. The method according to any one of implementation schemes P1 to P28, wherein the box body includes one or more pools directly or indirectly connected to the at least one opening, wherein the method further includes attaching a cover to the box body over one or more of the pools to form at least a partially enclosed chamber having each covered pool.
[0437] Implementation Scheme P30. The method according to Implementation Scheme P29, wherein the cover attached to the box body over the one or more pools includes a protective vent hood, the protective vent hood comprising: a vent membrane configured to contain liquid in the one or more pools and having through-holes formed therein to allow vapor to pass through the vent membrane; and a protective cover fixed to the vent membrane to block the through-holes and reduce or prevent vapor passage, wherein the protective cover can be peeled off from the vent membrane by a user before using the box.
[0438] Implementation scheme P31. The method according to implementation scheme P30, wherein the venting membrane of the venting hood includes blind tube holes that partially extend through the thickness of the venting membrane.
[0439] Other features and characteristics of the subject matter of this disclosure, as well as the methods of operation, the functions and combinations of related elements and components of the structure, and the economics of manufacture, will become more apparent when considering the following description with reference to the accompanying drawings, all of which form part of this specification, wherein like reference numerals designate corresponding portions in the various drawings. Attached Figure Description
[0440] The accompanying drawings, which are incorporated herein and form part of the specification, illustrate various embodiments of the subject matter of this disclosure. In the drawings, similar reference numerals denote the same or functionally similar elements.
[0441] Figure 1 This is the rear perspective view of the instrument as described in this article.
[0442] Figure 2 This is the front perspective view of the instrument.
[0443] Figure 3 This is an exploded top perspective view of an example of a fluid cell processed in the instrument described in this article.
[0444] Figure 4 This is a top plan view of the fluid box body.
[0445] Figure 5 This is a bottom plan view of the box body.
[0446] Figure 6 This is a top perspective view of the box itself.
[0447] Figure 7 This is a bottom perspective view of the box body.
[0448] Figure 8 This is a schematic cross-section of the fluid cell through the reaction / detection chamber of the fluid cell.
[0449] Figure 9 This is a bottom perspective view of the protective vent of the fluid chamber.
[0450] Figure 10 and Figure 10 "Detail A" shows the protective ventilator along... Figure 9 The cross section of line AA in the diagram.
[0451] Figure 11 This is an exploded top perspective view of the fluid cartridge's stopper, stopper ring, and syringe stopper.
[0452] Figure 12 This is the top perspective view of the blocking component.
[0453] Figure 13 This is the top view of the blocking component.
[0454] Figure 14 This is the bottom view of the blocking component.
[0455] Figure 15 This is a top perspective view of the sample chamber cap of the fluid cartridge.
[0456] Figure 16 This is a side view of the sample chamber cap.
[0457] Figure 17 It is along the sample chamber cap Figure 15 The cross section of line AA in the diagram.
[0458] Figure 18 The fluid chamber shows the body of the chamber. Figure 4 The cross section of line AA in the diagram.
[0459] Figure 19 The fluid chamber shows the body of the chamber. Figure 4 The local longitudinal section of line BB in the middle.
[0460] Figure 20 This is a perspective view of the syringe driver of the instrument.
[0461] Figure 21 It is a graph showing the motor current requirements and stop travel for four different fluid boxes.
[0462] Figure 22 The flowchart illustrates a method for controlling the position of a syringe stop using the motor requirements of a syringe drive module and the output of an encoder connected to the motor, and thus the volume of fluid drawn into the syringe body SB of the fluid cartridge.
[0463] Figure 23 This is a partial top perspective view showing the instrument's box support frame.
[0464] Figure 23A This is a perspective view of the box support bracket of an isolated box support frame.
[0465] Figure 24 This is a partial top perspective view showing the box support frame that supports the fluid box.
[0466] Figure 25 It is a schematic cross-section passing through the first and second thermal modules of the instrument and through the reaction / detection chamber of the box, wherein the first thermal module is in an elevated position relative to the second thermal module and the box.
[0467] Figure 26 It is a schematic cross-section passing through the first and second thermal modules of the instrument and through the reaction / detection chamber of the box, wherein the first thermal module is in a lowered position relative to the second thermal module and the box.
[0468] Figure 27 This is a top perspective view of the instrument's upper frame.
[0469] Figure 28 This is a side view of the upper rack.
[0470] Figure 29 This is a bottom perspective view of the upper rack.
[0471] Figure 30 This is a partial perspective view of the top of the instrument, showing the first (top) thermal module and the second (bottom) thermal module.
[0472] Figure 31 This is a top partial perspective view of the first (top) thermal module and the second (bottom) thermal module.
[0473] Figure 32 This is a partial perspective view of the bottom of the first and second thermal modules.
[0474] Figure 33 This is a top perspective view of the first thermal module.
[0475] Figure 34 This is a bottom perspective view of the first thermal module.
[0476] Figure 35 It is the passage of the first thermal module Figure 33 The cross-sectional view of line AA in the diagram.
[0477] Figure 36 This is a perspective view of the first thermal module, showing the first thermal component of the first thermal module in an exploded view.
[0478] Figure 37 This is an exploded perspective view of the second thermal component of the second thermal module.
[0479] Figure 38 This is a front view of the first and second thermal components of the second thermal module.
[0480] Figure 39 This is a left-side view of the second thermal component of the second thermal module.
[0481] Figure 40 This is a right-side view of the first thermal component of the second thermal module.
[0482] Figure 41 This is a top perspective view of the second thermal component of the second thermal module.
[0483] Figure 42 This is a partial top left perspective view of the instrument's contact detector when the first thermal module is in the raised position relative to the box.
[0484] Figure 43 This is a partial top left perspective view of the instrument's contact detector when the first thermal module is in a lowered position relative to the box and the contact detector is in contact with the box.
[0485] Figure 44 This is a partial top front perspective view of the instrument's contact detector.
[0486] Figure 45 A flowchart illustrating an implementation of a method for performing measurements using the instruments and fluid cell described herein is shown.
[0487] Figure 46 This is a curve showing the temperature distribution of the thermal cycler as described in this article.
[0488] Figure 47 This is a partial perspective view of a portion of the upper frame of the support box for displaying the instrument, the box having a rotary valve actuator attached to the upper frame.
[0489] Figure 48 yes Figure 47 The image shows a partial longitudinal section of the structure.
[0490] Figure 49 This is a top perspective view of the rotary valve actuator.
[0491] Figure 50 This is the cross-section of the rotary valve actuator.
[0492] Figure 51 yes Figure 50 The back side view of the cross section shown in the figure.
[0493] Figure 52 This is a perspective view of the valve actuator piston of a rotary valve actuator.
[0494] Figure 53 This is a perspective view of an implementation scheme for a cam-operated valve actuator.
[0495] Figure 54 yes Figure 53 Top perspective view of a cam-operated valve actuator.
[0496] Figure 55 It is along Figure 54 The cross section of line AA in the diagram.
[0497] Figure 56 It is along Figure 54 The cross section of line BB in the middle.
[0498] Figure 57 It is along Figure 54 The surface diagram of line CC in the diagram.
[0499] Figure 58 It is along Figure 54 The surface diagram of line DD in the diagram.
[0500] Figure 59 yes Figures 53 to 58 A front view of the valve actuator piston of a cam-operated valve actuator.
[0501] Figure 60 yes Figure 59 A perspective view of the valve actuator piston.
[0502] Figure 61 This is a perspective view of an alternative implementation scheme for a cam-operated valve actuator.
[0503] Figure 62 yes Figure 61 Top view of a cam-operated valve actuator.
[0504] Figure 63 It is along Figure 62 The cross section of line AA in the diagram.
[0505] Figure 64 It is along Figure 62 The cross section of line BB in the middle.
[0506] Figure 65 It is along Figure 62 The surface diagram of line CC in the diagram.
[0507] Figure 66 It is along Figure 62 The surface diagram of line DD in the diagram.
[0508] Figure 67 yes Figures 61 to 66 A front view of the valve actuator piston of a cam-operated valve actuator.
[0509] Figure 68 yes Figure 67 A perspective view of the valve actuator piston.
[0510] Figure 69 It is a partial cross-section through the reaction chamber and the thermally conductive laminated seal through the box body, where the top and bottom films are omitted in the attached drawings.
[0511] Figure 70 It is a top plan view of a laminated seal with a mask having an opening, wherein the mask is shown as crosshairs. Detailed Implementation
[0512] While the subject matter of this disclosure may be embodied in various forms, the following description and figures are intended only to disclose some of these forms as specific examples of the subject matter. Accordingly, the subject matter of this disclosure is not intended to be limited to the forms or embodiments described and shown. definition
[0513] Unless otherwise defined, all field terms, indexes, and other technical terms or terminology used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. All patents, applications, published applications, and other publications mentioned herein are incorporated herein by reference in their entirety. If any definition set forth in this section is contrary to or otherwise inconsistent with the definitions set forth in the patents, applications, published applications, and other publications incorporated herein by reference, the definitions set forth in this section shall prevail over those incorporated herein by reference.
[0514] Unless otherwise stated or implied by the context, as used herein, “a” or “an” means “at least one” or “one or more”.
[0515] References to "an implementation," "implementation," "further implementation," "example," "some aspects," "further aspects," "various aspects," etc., in the specification indicate that the described implementation, example, or aspect may include a particular feature, structure, or characteristic; however, each implementation covered by this disclosure may not necessarily include that particular feature, structure, or characteristic. Furthermore, such phrases do not necessarily refer to the same implementation, example, or aspect. Moreover, when a particular feature, structure, or characteristic is described in connection with an implementation, whether explicitly stated or not, such feature, structure, or characteristic is also a description in connection with other implementations, examples, or aspects.
[0516] This specification may use various terms describing relative spatial arrangement and / or orientation or direction when describing the position and / or orientation or direction of movement, force or other dynamic action of components, devices, locations, features, or a portion thereof. Unless specifically stated or indicated otherwise by the context of the specification, such terms, including but not limited to top, bottom, above, below, under, top of, upper, lower, left, right, front, back, below, beside, adjacent, between, horizontal, vertical, diagonal, longitudinal, transverse, radial, axial, clockwise, counterclockwise, etc., are used to conveniently refer to such components, devices, locations, features, or a portion thereof or movement, force or other dynamic action as shown in the drawings, and are not intended to be limiting.
[0517] Unless otherwise stated or implied by the context, the terms used herein to describe the physical and / or spatial relationship between a first component, structure or part thereof and a second component, structure or part thereof (such as attachment, connection, fixation, joining, linking, coupling or similar terms or variations thereof) shall cover the direct relationship of direct contact between the first component, structure or part thereof and the second component, structure or part thereof, or the presence of one or more intermediate components, structures or parts thereof between the first component, structure or part thereof and the second component, structure or part thereof.
[0518] Unless otherwise stated, any specific dimensions mentioned in this specification are merely examples of implementations of apparatus embodying various aspects of this disclosure and are not intended to be limiting.
[0519] Within the scope of use herein, whether explicitly indicated or not, the terms “about” or “approximately” apply to all numerical values and terms indicating specific physical orientations or relationships such as horizontal, vertical, parallel, perpendicular, concentric, or similar terms specified herein. The term generally refers to a series of numbers, orientations, and relationships that, in the context of this disclosure, would be considered by one of ordinary skill in the art to be a reasonable amount of deviation from the enumerated numerical values, orientations, and relationships (i.e., having an equivalent function or result). For example, and not intended to be restrictive, the term may be interpreted to include a deviation of ±10% from a given numerical value, orientation, or relationship, provided that such deviation does not alter the final function or result of said value, orientation, or relationship. Thus, in some cases, as would be understood by one of ordinary skill in the art, a value of about 1% or approximately 1% may be interpreted as a range from 0.9% to 1.1%.
[0520] Within the scope of this document, the term "proximity" means close (spatial proximity) or adjacent. Proximity objects or portions thereof may be spaced apart from each other, or may be in actual or direct contact with each other. In some instances, proximity objects or portions thereof may be connected to each other or may be integrally formed with each other.
[0521] Within the scope of use herein, the terms “substantially” and “basically” refer to a considerable degree or extent. When used in conjunction with, for example, an event, situation, characteristic, or property, the terms may refer to instances in which the event, situation, characteristic, or property occurs precisely as described herein, and instances in which the event, situation, characteristic, or property is close to approximately occurring, taking into account typical tolerance levels or variability of the embodiments described herein.
[0522] Within the scope of use herein, the terms “optional” and “optionally” or the term “may” (e.g., in phrases such as “may include,” “may include,” “may produce,” “may provide,” or similar phrases) mean that the components, structures, elements, events, situations, characteristics, properties, etc., subsequently described may be included or present, or may not be included or present, and describes instances of components, structures, elements, events, situations, characteristics, properties included or present, as well as instances of components, structures, elements, events, situations, characteristics, properties, etc., not included or present therein.
[0523] Within the scope of this document, the terms “first,” “second,” and similar terms preceding the names of elements (e.g., components, devices, positions, features, or a portion thereof, or the direction of movement, force, or other dynamic action) are used for identification purposes to distinguish between similar elements and are not intended to necessarily imply order or hierarchy. Furthermore, the terms “first” and “second” are not intended to exclude the inclusion of additional similar elements. Moreover, unless the context otherwise requires, the use of the term “first” preceding the name of an element (e.g., components, devices, positions, features, or a portion thereof, or the direction of movement, force, or other dynamic action) does not necessarily imply or require the presence of additional (e.g., “second,” “third,” etc.) such elements.
[0524] Within the scope of this document, the terms or phrases “configured to,” “adapted to,” “operable as,” “constructed and arranged as,” and similar terms mean that the purpose of the terms or phrases includes, constitutes, or otherwise encompasses the necessary (multiple) structures, (multiple) mechanisms, (multiple) arrangements, (multiple) components, (multiple) materials, (multiple) algorithms, (multiple) circuits, programming, etc., to automatically or permanently, or selectively when required to do so, perform one or more specified tasks or achieve specified outputs or characteristics.
[0525] Within the scope of this document, the term "amplification reaction" refers to a procedure used to produce multiple copies of a specific segment of a nucleic acid. Amplification reactions can be isothermal or require repeated cycles between different temperatures, such as those required by polymerase chain reaction (PCR).
[0526] Within the scope of this document, the term "analyte" refers to a molecule or substance that is detected or analyzed in an assay. Examples of analytes include nucleic acids, proteins (e.g., antibodies, peptides, and prions), and antigens.
[0527] Within the scope of this document, the term "determination" refers to a procedure for detecting and / or quantifying an analyte in a sample. This involves contacting a sample containing or suspected of containing an analyte with one or more reagents and subjecting it to conditions that allow the generation of a detectable signal, which provides useful information about the presence of the analyte in the sample or the amount of the analyte (e.g., mass or concentration).
[0528] Within the scope of this document, the term "analyst" refers to an automated instrument capable of performing one or more steps of determination, including the step of determining the presence or absence of one or more analytes suspected of being present in a fluid sample.
[0529] Within the scope of this document, the term "molecular assay" refers to a procedure for specifically detecting and / or quantifying a target molecule, such as a specific nucleic acid. A sample containing or suspected of containing a target molecule is contacted with one or more reagents comprising at least one reagent specific to said target molecule and subjected to conditions that allow the generation of a detectable signal providing useful information about the presence of the target molecule. For example, in cases where the molecular assay includes an amplification reaction (such as polymerase chain reaction (PCR)), the reagents include primers that can be specifically targeted at the target nucleic acid, and the generation of a detectable signal can be at least partially achieved by providing a labeled probe (e.g., a fluorescently labeled probe) that hybridizes in a target-specific manner with an amplicon generated by the primers in the presence of the target. Alternatively, the reagents may include an intercalation dye (e.g., SYBR® Green) for detecting the formation of double-stranded nucleic acids.
[0530] Within the scope of this article, the term "point-of-care testing" (POCT), sometimes referred to as near-patient testing, refers to testing performed at a site close to the patient's care or treatment. This can be in a hospital, a doctor's office, or a field testing setting. Unlike high-throughput systems, POCT systems are generally small and easily portable. Most POCT systems are capable of running measurements on a single sample or a limited number of samples simultaneously.
[0531] Within the scope of this document, the term "reagent" refers to any substance or mixture involved in the assay, other than the sample material and the product being measured. Examples of reagents used in molecular assays include nucleotides, enzymes, primers, probes, and salts.
[0532] Within the scope of use herein, the term "receiver" or "fluid receiver" refers to any type of fluid container configured to contain a sample or another fluid (collectively referred to herein as "fluid"), including, for example, tubes, vials, cuvettes, pools or boxes, or other articles having one or more pools or chambers formed therein or attached thereto, microtiter plates, etc. Tubes may be cylindrical (i.e., circular in cross-section) or non-cylindrical and may have flat or rounded closed ends. Non-limiting examples of receivers include, for example, Novodiag® Sample Buffer and Collection Tubes (Mobidiag Oy, Espoo, Finland) and Aptima® Multiplex Test Swab Collection Kit (Hologic, Inc., Marlborough, Massachusetts).
[0533] Within the scope of this document, the term "sample" means any substance suspected of containing at least one analyte of interest. Analytes of interest can be, for example, nucleic acids, proteins, chemicals, etc. Substances can be derived from any source, including animals, industrial processes, the environment, water sources, food products, or solid surfaces (e.g., surfaces in medical facilities). Substances obtained from animals can include, for example, blood or blood products, urine, mucus, sputum, saliva, semen, tears, pus, feces, nasopharyngeal or genitourinary specimens obtained by swabs or other collection devices, and other bodily fluids or materials. The term "sample" will be understood to mean a specimen in its natural form or at any stage of processing.
[0534] Within the scope of this document, the terms “thermal contact” or “thermal connectivity” mean the ability to allow the transfer of thermal energy between two systems or bodies at different temperatures. The two systems or bodies may be in direct physical contact, allowing thermal energy transfer to occur directly from one system or body to the other, or an intermediate material comprising air may be arranged between the two systems or bodies, allowing thermal energy transfer to occur through said intermediate material.
[0535] Within the scope of this document, the term "unit dosage form" means an amount sufficient to perform a single assay. That is, in contrast to bulk reagents provided in amounts that can be used to perform multiple assays, a "unit dose" or "unitized" reagent is an amount of reagent that can be used for a single assay (which may be designed to determine the presence of one or more analytes).
[0536] A "fluid cartridge" is an apparatus comprising a fluid network of two or more chambers containing fluid, the fluids being fluidly interconnected or fluidly interconnectable via one or more fluid channels. The apparatus is configured to interface with a processing instrument or analyzer for performing one or more treatments on the fluid contained within the cartridge, including, for example, one or more of the following: applying positive or negative pressure to the cartridge; applying physical pressure to at least one chamber to cause the chamber to collapse at least partially; or actuating a pump mechanism operatively coupled to the cartridge to enable fluid movement between chambers within the fluid network; actuating or otherwise altering a flow control mechanism (such as a valve) to change the flow control mechanism between an open state that allows fluid flow and a closed state that blocks fluid flow; heating and / or cooling the fluid in one or more chambers of the cartridge; and detecting and recording signals based on optical emission from the fluid contained in one or more chambers of the cartridge. Detailed description of the attached figures
[0537] Figure 1 and Figure 2 The internal components of an instrument 10 as described herein are shown. This instrument receives and operates a test platform (such as a fluid cartridge (i.e., a device configured to be placed within and interfaced with a processing instrument and including reagent and sample storage and fluid disposal components such as fluid flow channels and flow control valves)) to process samples on or within the test platform (e.g., to perform assays (such as molecular assays) and collect data on the results of the assays). Instrument 10 includes components for applying thermal energy to one or more detection regions of the test platform, components for transmitting optical signals to and / or from the reaction / detection regions(s), and components for actuating a syringe pump within the test platform. Figure 1 This is the rear perspective view of instrument 10, and Figure 2 This is a front perspective view of instrument 10. Instrument 10 can be an on-the-fly testing system for providing sample-to-result testing using a disposable fluid cartridge, the disposable fluid cartridge comprising interconnected chambers (or pools) and a reaction chamber that can be pre-packaged in unit doses containing all the reagents required to perform the desired test. The fluid cartridge can be a closed system that minimizes the chance of contamination.
[0538] Typically, such an instrument will include a housing, within which the internal components will be enclosed, but from Figure 1 The casing is omitted, allowing the internal components to be seen.
[0539] like Figure 1 and Figure 2As shown, the test platform (e.g., fluid chamber 500) is located within instrument 10, and the internal components of the instrument can typically be divided into a first frame or upper frame 300 (referring to those internal components located above chamber 500) and a second frame or lower frame 400 (referring to those internal components located below chamber 500). Chamber 500 may be a microfluidic chamber, meaning that at least a portion of any fluid passage, channel, chamber, pool, reaction chamber, etc., in which fluid flows and / or is retained is geometrically constrained to a small scale (e.g., submillimeter), at which the surface forces acting on the fluid satisfy or exceed volume forces. Upper frame 300 may include syringe actuator 360, which is configured to actuate a syringe plunger coupled to a syringe stop within chamber 500, as described below.
[0540] Fluid box
[0541] exist Figures 3 to 19 An embodiment of the fluid cartridge 500 and its components is shown in the figure. Figure 3 An exploded top perspective view of the fluid cartridge 500 is shown. The cartridge 500 includes a cartridge body 502, a first (e.g., top) membrane 512, a second (e.g., bottom) membrane 530, an elastomeric stop 540, a stop ring 550, a stop 570, a sample filter 538, a purification column insert 536 that can be in the form of a disc for positioning and holding a purification column (e.g., a silica column), a cap 516, and a protective vent 560. For convenience and consistency with the example shown in the figures, membrane 512 will be referred to herein as the top membrane, and membrane 530 as the bottom membrane. A syringe driver 360 is coupled to instrument 10 (see description below). Figure 20The plunger 362 includes a plunger head 364 and a plunger rib 366, the plunger head being received within a recess formed in a stop 540, the plunger rib engaging a stop 570 as described below. The cartridge body 502 of the fluid cartridge 500 includes: (i) a plurality of chambers or functional pools W1 to W12 and SB, which contain or are configured to receive materials (e.g., sample materials, reagents, buffer solutions, etc.) used in performing assays (e.g., molecular assays); (ii) chambers or functional pools in which two or more materials can be combined and mixed; (iii) chambers or functional pools for receiving and retaining waste materials; and (iv) reaction / detection chambers 510a1, 510a2, 510b1, 510b2 (i.e., detection areas), in which reactions can occur and / or detectable signals emitted by reactions within the chambers can be detected. In the context of this disclosure, although the terms “pool” and “chamber” may be used interchangeably in some descriptions, generally, the term “pool” refers to, but is not limited to, an open reservoir or recess (such as pools W1 to W12 and SB) formed in the housing body 502, and the term “chamber” refers to, but is not limited to, a pool in the housing body 502 that is at least partially enclosed, for example by a first membrane 512, a second membrane 530, and / or a cover 560, to form a at least partially enclosed compartment or space. More than one of the functions of containing, combining, reacting, and detecting may occur within one or more functional chambers of the housing 500. As described below, the functional chambers within the housing may be fluidly interconnected by fluid channels or conduits, and the housing includes one or more fluid flow control valves that may be selectively actuated, for example, by a valve actuator of the instrument 10, to controllably permit or prevent fluid flow within the fluid channels operatively associated with the valves. The example shown has four reaction / detection chambers 510a1, 510a2, 510b1, and 510b2, which are arranged in two pairs (or sets or groups) 510a1, 510a2 and 510b1, 510b2. In other examples, the box has fewer or more than four reaction / detection chambers. For example, the box may have one or more sets or three aggregated reaction / detection chamber sets.
[0542] The box body 502 has a first (e.g., top) surface 501 and a second (e.g., bottom) surface 503. For convenience and consistency with the example shown in the accompanying drawings, surface 501 will be referred to herein as the top surface, and surface 503 will be referred to herein as the bottom surface. The box body 502 may be injection molded from a thermoplastic polymer material, and preferably from polypropylene (PP), such as cyclic olefin copolymers (COC) or cyclic olefin polymers (COP), including polycarbonate, polyacrylamide, polyethylene, polymethyl methacrylate (PMMA), polydimethylsiloxane (PDMS), and polyvinyl chloride (PVC). In some embodiments, the box body 502 is formed by stereolithography or by sintering. The box body 502 may be made of an opaque material.
[0543] like Figure 4 (Top plan view of box body 502) and Figure 5 As shown in the bottom plan view of the housing body 502, the housing body 502 includes a plurality of through-holes H1 to H32 extending between a top surface 501 and a bottom surface 503 to fluidly connect components from one surface to the other. The housing body 502 includes a plurality of bottom recesses G1 to G20 formed in the bottom surface 503 and a plurality of top recesses G21 to G32 formed in the top surface 501. Each of the recesses G1 to G32 may have a depth between 0.01 mm and 0.5 mm, preferably between 0.2 mm and 0.4 mm, and most preferably about 0.3 mm, and may have a width of about 0.5 mm. Each of the through-holes H1 to H18 is associated with a corresponding valve V1 to V18, the corresponding valve comprising a cylindrical recess formed in the bottom surface 503 of the housing body 502, and the cylindrical recess is generally arranged coaxially with respect to the associated through-hole and has a diameter larger than that of the associated through-hole. In one example, the recess associated with each of valves V1 to V18 may have a diameter between 1 mm and 10 mm, preferably between 2 mm and 8 mm, preferably about 4 mm, and a depth between 0.02 mm and 0.4 mm, preferably between 0.05 mm and 0.15 mm, and most preferably about 0.1 mm. One or both of the recesses G1 to G32 terminate at the associated valves V1 to V18. Through holes H1 to H10 are also associated with chambers W1 to W10, through holes H11 and H12 are associated with chamber W6, through hole H19 is associated with chamber W11, and through hole H20 is associated with chamber W12. Through holes H21 to H32 are not directly associated with valves or chambers and provide connection between the recess or other feature on the top surface 501 and the recess or other feature on the bottom surface 503. The cartridge body 502 also includes central through holes H1c to H10c arranged in a circular pattern within the pool SB (injection cartridge body).
[0544] The through-holes H1 to H32 and H1c to H10c, valves V1 to V18 and associated recesses formed in the housing body 502, as well as the bottom recesses G1 to G21 and top recesses G22 to G32, form a network of fluid channels and fluid control valves in these channels. For this purpose, it is necessary to close the through-holes, recesses, and grooves that are open to the top surface 501 or bottom surface 503 of the housing body 502. The bottom film 530 is fixed to the bottom surface 503 of the housing body 502 to cover the bottom recesses G1 to G20 to form corresponding channels (which may be microfluidic channels), to cover the recesses of valves V1 to V18 to form corresponding valves, to cover the central through-holes H1c to H10c, and the through-holes H19 to H32 flush with the bottom surface 503. The bottom film 530 may comprise a material similar to the housing body 502, including, for example, polypropylene (PP). The bottom film 530 may include a thermoplastic film having a thickness between 0.1 mm and 0.2 mm (100 µm to 200 µm), which is bonded or welded to the surface of the bottom surface 503 by thermal welding technology (e.g., by laser welding), bonding, adhesive or chemical bonding methods.
[0545] Valves V1 to V18 are formed of a bottom diaphragm 530, which may be deformable and extends across each opposing recess of an annular valve seat, the annular valve seat being defined respectively between the recess of each valve V1 to V18 and the associated through-hole H1 to H18 of the valve. A single valve seat 505 between the recess of valve V2 and the associated through-hole H2 is... Figure 7 The text is marked in the original. In one example, the surface of the deformable bottom film 530, disposed opposite the recesses of valves V1 to V18, is approximately planar and parallel to the bottom surface 503 of the housing body 502 when undeformed, and is spaced apart from the valve seats between the recesses and through-holes. It can be deformed by an external actuator that partially pushes the film into the recesses. The deformed bottom film 530 contacts each valve seat of valves V1 to V18, blocking the associated through-holes H1 to H18, the diameter of which is smaller than the diameter of each associated recess, such that the film contacts the valve seat and seals the associated through-hole.
[0546] The top film 512 can be fixed to the top surface 501 of the housing body 502, for example, by thermal welding, adhesive bonding, or chemical bonding, to close the top grooves G21 to G32 flush with the top surface 501 in the same way that the bottom film 530 closes the bottom grooves G1 to G20 to form corresponding channels, thus forming corresponding channels (which may be microfluidic channels). The top film 512 can be made of a material similar to the housing body 502 (e.g., polypropylene) and can have a thickness of about 0.1 mm.
[0547] Box 500 may include processing areas 594a, 594b (see Figure 4 , Figure 5 , Figure 7 In one example, each of the processing regions 594a and 594b includes a microarray slide (or biochip) adhered to the bottom surface 503 of the cartridge body 502 within a recessed cavity, which, when covered, for example, by a bottom film 530, forms a detection chamber for nucleic acid analysis. The instrument 10 may include means (not shown) for optically exciting the microarray slide and means for optically detecting a microarray image (not shown) representing an analyte of interest (e.g., nucleic acid) of the sample being analyzed in the cartridge. For further description of the microarray slide, see, for example, U.S. Patent No. 10,654,039.
[0548] refer to Figure 4 and Figure 5Bottom recesses G1 to G10 extend between central through-holes H1c to H10c and recesses associated with each of valves V1 to V10, respectively. Each of valves V1 to V10 is associated with through-holes H1 to H10. Each of the through-holes H1 to H10 associated with valves V1 to V10 connects chambers W1 to W10 to bottom recesses G1 to G10, respectively. In this context, connection to or through a top or bottom recess means connection of a corresponding channel formed by or through each recess when covered by a top or bottom film 512 or 530. Through-hole H11 associated with valve V11 connects chamber W6 to bottom recess G12. Through-hole H12 associated with valve V12 connects chamber W6 to bottom recess G13. The through-hole H13 associated with valve 13 will connect the bottom recess G15 of chambers 510b1 and 510b2 to the top recess G21. The through-hole H14 associated with valve V14 will connect the bottom recess G16 of chambers 510a1 and 510a2 to the top recess G22. The through-hole H15 associated with valve V15 will connect the bottom recess G17 to the top recess G29, which merges with the top recess G30. The through-hole H16 associated with valve V16 will connect the bottom recess G18 to the top recess G30. The through-hole H17 associated with valve V17 will connect the bottom recess G19 to the top recess G31. The through-hole H18 associated with valve V18 will connect the bottom recess G20 to the top recess G32, which merges with the top recess G31. The through-hole H19 will connect the bottom recess G11 to chamber W11. The through-hole H20 will connect the bottom recess G14 to chamber W12. Through hole H21 connects bottom recess G11 to top recess G23. Through hole H22 connects bottom recess G12 to top recess G21. Through hole H23 connects bottom recess G13 to top recess G22. Through hole H24 connects bottom recess G14 to top recess G24. Through hole H25 connects bottom recess G17 to top recess G25 connected to chamber 510b2. Through hole H26 connects bottom recess G18 to top recess G26 connected to chamber 510b1. Through hole H27 connects bottom recess G19 to top recess G27 connected to chamber 510a2. Through hole H28 connects bottom recess G20 to top recess G28 connected to chamber 510a1. Through hole H29 connects recess G30 to the processing area 594b of the box. Through hole H31 connects processing area 594b to top recess G23, which is connected via through hole H21 to bottom recess G11 of chamber W11 (e.g., waste chamber) via through hole H19. Through hole H30 connects top recess G31 to processing area 594a of the box.Through-hole H32 connects processing area 594a to top recess G24, which is connected via through-hole H24 to bottom recess G14, which is connected via through-hole H20 to chamber W12 (e.g., waste chamber). Therefore, when valve V8 is open, reaction chamber 510a1 is connected to processing area 594a via recesses G28, G20, G32, and G31. When valve V17 is open, reaction chamber 510a2 is connected to processing area 594a via recesses G27, G19, and G31. When valve V15 is open, reaction chamber 510b2 is connected to processing area 594b via channels G25, G17, G29, and G30. When valve V16 is open, reaction chamber 510b1 is connected to processing area 594b via channels G26, G18, and G30.
[0549] Such as a schematic cross-sectional view of box 500. Figure 8 As shown, chambers 510a1, 510a2, 510b1 and 510b2 are defined by openings formed in the box body 502, which extend between the top surface 501 and the bottom surface 503 and are closed by the bottom film 530 and the top film 512. Reaction / detection chambers 510a1, 510a2, 510b1, and 510b2 receive reaction mixtures prepared from the contents of one or more of chambers W1 to W10. The reaction mixtures are exposed to heat (e.g., isothermal or thermal cycling distribution) within chambers 510a1, 510a2, 510b1, and 510b2 by contacting the top portions of adjacent chambers 510a1, 510a2, 510b1, and 510b2 of the cartridge 500 with a top heater, and by contacting the bottom portions of adjacent chambers 510a1, 510a2, 510b1, and 510b2 of the cartridge 500 with a bottom heater. Reactions (e.g., amplification reactions) occur within chambers 510a1, 510a2, 510b1, and 510b2. The reaction mixture within chambers 510a1, 510a2, 510b1, and 510b2 may include a detectable probe that emits a detectable optical signal upon hybridization with a molecule of interest during the reaction, for example, a fluorescence signal with an emission wavelength when emitted by light of a certain excitation wavelength. For this purpose, at least one wall of chambers 510a1, 510a2, 510b1, and 510b2 may be transparent or translucent. For example, if the housing body 502 is made of an opaque material, the top film 512 may be transparent or translucent, or at least a portion of the top film 512 covering chambers 510a1, 510a2, 510b1, and 510b2 may be transparent or translucent to allow excitation signals to be delivered to the chambers from above and to allow emission signals to be detected from above the chambers.
[0550] To promote uniform heat distribution above chambers 510a1, 510a2, 510b1, and 510b2, the bottom film 530 may include a layer of thermally conductive material, such as a metal foil (e.g., aluminum), which is disposed on the bottom surface 503 of the housing body 502, at least adjacent to chambers 510a1, 510a2 and adjacent to chambers 510b1 and 510b2. Figure 8 As shown, the lower film 530 may have cutouts 531a and 531b on chambers 510a1, 510a2 and chambers 510b1, 510b2, respectively. A thermally conductive laminated seal 532a is disposed within the cutout 531a and attached to the housing body 502 above chambers 510a1, 510a2, and a thermally conductive laminated seal 532b is disposed within the cutout 531b and attached to the housing body 502 above chambers 510b1, 510b2. The cutouts 531a, 531b and the associated thermally conductive laminated seals 532a, 532b may be rectangular (e.g.,...). Figure 3 (as shown in the diagram), circular, elliptical, or any desired shape. When the reaction / detection chambers are arranged as spatially separated groups of chambers (where a “group” may include one or more chambers), discrete thermally conductive laminated seals may be provided to cover each group. For example, when the chambers 510a1, 510a2 and 510b1, 510b2 of the fluid cartridge 500 are arranged as spatially separated groups (e.g., pairs), two separate thermally conductive laminated seals are provided: a laminated seal 532a for covering groups 510a1, 510a2 and a laminated seal 532b for covering groups 510b1, 510b2.
[0551] In one example, each thermally conductive laminated seal 532a, 532b includes a plastic layer 533 (e.g., polypropylene) to which a conductive foil layer 534 is laminated. Suitable commercially available products include Thermo-Fisher AB 3599, available from Thermo-Fisher Scientific in Waltham, Massachusetts. The conductive foil layer 534 may also be optically reflective (e.g., aluminum or metallized PET film). The plastic layer 533 and the conductive foil layer 534 can be bonded together by a suitable adhesive or other means suitable for securing the plastic to the foil. In one example, for a total thickness of 70 µm to 100 µm for each thermally conductive laminated seal 532a, 532b, the conductive foil layer 534 has a thickness of 60 µm to 80 µm, and the plastic layer 533 has a thickness of 10 µm to 20 µm. As noted herein, the bottom film 530 may have a thickness of approximately 0.1 mm to 0.2 mm (100 µm to 200 µm). In another example, each thermally conductive laminated seal 532a, 532b includes a second plastic layer (not shown) attached to the opposite side of the conductive foil layer 534.
[0552] Each thermally conductive laminated seal 532a, 532b is attached to the housing body 502 by heat sealing, ultrasonic welding, adhesives, or other suitable methods for bonding the plastic layer 533 of each thermally conductive laminated seal 532a, 532b to the housing body 502 to prevent fluid leakage from chambers 510a1, 510a2, 510b1, 510b2. In this regard, for heat sealing or ultrasonic welding, the housing body 502 may include an energy director to facilitate the heat sealing or ultrasonic welding process. An energy director is a component or feature in heat sealing applications that helps focus and control the flow of energy (heat or vibration) to the area where a seal is being created. Examples of energy directors include raised features (e.g., ribs) adjacent to or surrounding each of chambers 510a1, 510a2, 510b1, 510b2 to form narrow edges (e.g., dome-shaped or knife-edge (triangular) sections) that focus energy at the edges and promote localized material melting at the edges to facilitate sealing of laminated seals 532a, 532b. Conductive laminated seals 532a, 532b are heat-sealed by melting and fusion of the plastic layer 533 of the energy directors surrounding chambers 510a1, 510a2, 510b1, 510b2 and each of the laminated seals 532a, 532b.
[0553] Figure 69 The partial cross-section of the box body 502 is through the reaction chambers 510a1, 510a2 and the thermally conductive laminated seal 532a, wherein the top film 512 and the bottom film 530 are omitted in the figure. Figure 69An example of an energy director in the form of a blade (triangular) rib 535a1 surrounding reaction chamber 510a1 and a blade (triangular) rib 535a2 surrounding reaction chamber 510a2 is shown. In one example, energy directors 535a1 and 535a2 have a base width of approximately 0.3 mm and a tip height of approximately 0.26 mm. Similar energy directors (not shown) may surround reaction chambers 510b1 and 510b2. Energy directors 535a1 and 535a2 in Figure 69 They are not necessarily shown to scale and are shown in their peaked state during the heat-sealing process before they are melted and melted with the plastic layer 533 of the thermally conductive laminated seal 532a.
[0554] In one example, the heat-sealing temperature is approximately 165ºC to 180ºC. The lower end of this temperature range is fixed by the melting temperature of the plastic layer 533 (e.g., the melting temperature of polypropylene), but the upper end of this range can be higher than 180ºC. In this example, the sealing pressure is approximately 30 psi to 50 psi or greater. The sealing time is approximately 1.0 second to 1.2 seconds, but can also be as long as 5.0 seconds to 10.0 seconds.
[0555] The housing 502 may include quality control features to ensure that the laminated seals 532a, 532b have been properly heat-sealed to the housing 502—for example, to ensure that the energy conductors 535a1 and 535a2 have melted and fused with the plastic layer 533 of the thermally conductive laminated seal 532a during the heat-sealing process. Figure 69 As shown, such quality control features may include one or more inspection holes 537, 539, which extend through the housing body 502 adjacent to chambers 510a1, 510a2 and within the surface area to be covered by the laminated seal 532a. In one example, inspection holes 537, 539 have a diameter of approximately 0.6 mm. Similar inspection holes (not shown) extending through the housing body 502 may be provided adjacent to chambers 510b1, 510b2 and within the surface area to be covered by the laminated seal 532b. Each inspection hole is at least partially surrounded by an energy director that melts when the laminated seals 532a, 532b are heat-sealed to the housing body 502. Inspection hole 537 is surrounded by an energy director 541, and inspection hole 539 is surrounded by an energy director 543. Energy directors 541 and 543 are in... Figure 69 They are not necessarily shown to scale, and are shown in their pointed state during the heat sealing process before they are melted and melted with the plastic layer 533 of the thermally conductive laminated seal 532a and before the energy guide melts into the inspection ports 537, 539.
[0556] If the heat seal is completed correctly, the energy guides around the inspection holes will melt and flow into the inspection holes, thereby closing the inspection holes (fully or partially). If the heat seal is not completed correctly, such that the energy guides around the inspection holes do not completely melt and flow into the inspection holes, the inspection holes will remain open or substantially open (i.e., not closed, substantially closed, or at least partially closed). If the energy guides 541 and 543 around the inspection holes 537 and 539, respectively, fill, substantially fill, or at least partially fill the holes after the heat seal process, it can be inferred that the energy guides 535a1 and 535a2 around the reaction chambers 510a1 and 510a2 have also been correctly melted and fused with the plastic layer 533. The degree of closure of the inspection holes considered necessary for successful melting can vary depending on application requirements. Conversely, if the energy directors 541 and 543 surrounding inspection holes 537 and 539, respectively, are not filled, substantially filled, or at least partially filled with one or more of the holes after the heat-sealing process, it can be inferred that the energy directors 535a1 and 535a2 surrounding reaction chambers 510a1 and 510a2 may not have melted properly and fused with the plastic layer 533. Therefore, it can be determined whether the heat sealing was correctly completed by checking whether each inspection hole is open or closed after the heat-sealing process (e.g., using a machine vision device). If the inspection hole is covered by molten energy directors, it will appear black during visual inspection, and if the inspection hole is not completely covered, it will appear gray or silver (i.e., the color of the conductive aluminum foil layer 534).
[0557] Energy guides 541 and 543 surrounding inspection holes 537 and 539 respectively can have the same size and shape as energy guides 535a1 and 535a2 surrounding reaction chambers 510a1 and 510a2 respectively, or can have different sizes and / or shapes. If the inspection hole energy guides have the same dimensions as the reaction chamber energy guides, it can be assumed that the two energy guides react in a manner similar to heat-sealing conditions. The preferred size of the energy guides can be related to the size of the inspection holes—that is, the larger the inspection hole, the larger the energy guide, to ensure that the melting and molten energy guides (fully or partially) cover the inspection hole. Such energy guide features can be molded into the cartridge body 502, such as... Figure 69 As shown in the image.
[0558] The methods and techniques described above for attaching laminated seals 532a, 532b to a housing body 502 are not limited to their application to seals with a thermally conductive layer, but can be used to attach any type of plastic film or laminate with a plastic layer to a plastic body, such as a housing body 502.
[0559] The conductive foil layer 534 of each thermally conductive laminated seal 532a, 532b is an effective thermal conductor, which, combined with a relatively thin plastic layer (such as polypropylene) used as an insulator, promotes rapid conductive heat transfer from the heaters arranged below the chambers 510a1, 510a2, 510b1, 510b2, thereby rapidly heating the chambers by the heaters arranged below the chambers, and promotes uniform heat distribution to minimize the thermal gradient throughout the chambers 510a1, 510a2, 510b1, 510b2.
[0560] In some examples, the conductive foil layer 534 can improve the intensity and accuracy of optical emission signal detection from chambers 510a1, 510a2, 510b1, and 510b2. The conductive foil layer 534 of each thermally laminated seal 532a, 532b can provide a reflective surface to increase the intensity of the optical emission signal. An optical excitation signal introduced from above each of chambers 510a1, 510a2, 510b1, and 510b2 passes through the reaction mixture within the chamber and excites the probe-associated mark. Then, as the optical excitation signal is reflected away from the conductive foil layer 534 at the bottom of each chamber, the reflected excitation signal again passes through the reaction mixture within the chamber and again excites the probe-associated mark. Furthermore, the optical emission signals collected from above chambers 510a1, 510a2, 510b1, and 510b2 will be enhanced because both optical signals emitted directly toward the top of each chamber and optical signals emitted toward the bottom of each chamber and reflected toward the top of the chamber by the conductive foil layer 534 at the bottom of the chamber can be collected.
[0561] Furthermore, the laminated seals can increase the accuracy of the emitted signals collected from chambers 510a1, 510a2, 510b1, and 510b2. A relatively thick transparent or translucent thin film layer (e.g., a thickness of 100 µm to 200 µm, such as the bottom film 530) directly covering chambers 510a1, 510a2, 510b1, and 510b2 can serve as an optical emitter (i.e., a light tube) that can laterally transmit optical signals from one chamber to adjacent chambers (e.g., between chambers 510a1 and 510a2, and between chambers 510b1 and 510b2). Such inter-chamber optical transmission is reduced or eliminated by thermally conductive laminated seals 532a and 532b having a plastic layer 533 that can be as thin as 10 µm to 20 µm, directly covering chambers 510a1, 510a2, 510b1, and 510b2. In addition, metal foils such as aluminum foil are impermeable to water, thereby preventing vapor from being transferred to or from chambers 510a1, 510a2, 510b1, 510b2, to enhance the stability of the dried (dehydrated or lyophilized) reagents stored in the chambers.
[0562] The reagents required to perform a specified reaction within reaction chambers 510a1, 510a2, 510b1, and 510b2 may be pre-applied in wet form and then dried onto the interior-facing surfaces of the laminated seals 532a and 532b (i.e., the outer surface of the plastic layer 533 of the laminated seals 532a and 532b). Before or after sealing the laminated seals 532a and 532b onto the cartridge body 502 above chambers 510a1, 510a2, 510b1, and 510b2, such reagents, which may include dehydrated or lyophilized components for performing PCR (e.g., Taq DNA polymerase, dNTPs, buffer, MgCl2, and optional primers and / or probes), may be applied in wet form to the plastic layer 533 and then dried in situ to form dried reagent “spots.” Figure 8 Reagent spots 511a1, 511a2, 511b1, and 511b2 are shown in reaction chambers 510a1, 510a2, 510b1, and 510b2, respectively. Reagent spots 511a1, 511a2, 511b1, and 511b2... Figure 8 The reagent spots are not necessarily drawn to scale, and their exaggerated thicknesses are shown for visibility. Each of reagent spots 511a1, 511a2, 511b1, and 511b2 may be the same reagent or a combination of reagents, or one or more reagent spots may be different reagents or combinations of reagents from the other reagent spots.
[0563] To facilitate the process of applying reagent spots to and then drying them onto the surface of plastic layer 533 (referred to as "spotting"), the surface of plastic layer 533 may be treated to increase its hydrophilicity or wettability. To avoid wasting reagent and to ensure that the reagent is exposed to the reaction mixture introduced into reaction chambers 510a1, 510a2, 510b1, 510b2, it is preferable that the reagent is spotted onto only the portions of plastic layer 533 that are aligned with chambers 510a1, 510a2, 510b1, 510b2. Accordingly, the surface treatment to increase the hydrophilicity of the surface may be limited to one or more portions of the surface where the desired reagent spotting is desired (i.e., aligned with the positions of chambers 510a1, 510a2, 510b1, 510b2), rather than the entire surface.
[0564] In one example, the outer surface of the plastic layer 533 is masked with a plastic strip having openings corresponding to the desired reagent spot locations in chambers 510a1, 510a2, 510b1, and 510b2. This in Figure 70 The image shows a laminated seal 532a with a mask 515 (shown as crosshairs) on a plastic layer having openings 513a1 and 513a2. Figure 70In the example shown, openings 513a1 and 513a2 are smaller than chambers 510a1 and 510a2, the outline of which is superimposed on mask 515 with dashed lines. In one example, a suitable mask material is a polyester film with a typical thickness of 50 ± 2 µm (as measured by ASTM D-3652 test method), the polyester film having an acrylic adhesive with a typical thickness of 7 ± 2 µm (as measured by ASTM D-3652 test method), the acrylic adhesive having a stainless steel adhesion value of 6 g / in to 12 g / in (as measured by ASTM D-3330 – 180° peel test method). Suitable materials are available from M&C Specialties in Southampton, Pennsylvania.
[0565] Alternative mask materials include materials used as electrical insulators, including various types of plastics, rubber, ceramics, or glass. Suitable adhesives have low adhesion, allowing them to be easily peeled off from the surface of the plastic layer 533 without leaving any residue on the surface after mask removal. A preferred feature of the mask is that it adheres to the surface with minimal air gaps. The inventors have used masks with a thickness of approximately 50 µm, although thicker masks are expected to function equally or better.
[0566] Next, the surface is subjected to corona treatment, whereby corona discharge is used to treat only the exposed areas of the outer surface of the plastic layer 533 exposed by the openings 513a1, 513a2 in the mask 515, thereby changing the exposed surface to increase the hydrophilicity of the surface, while the masked areas of the outer surface 533 covered by the mask 515 are not treated with corona discharge and remain relatively hydrophobic.
[0567] An example of a corona discharge device already used by the inventors is the BD-20AC laboratory corona processor, available from Electro-Technic Products, Chicago, Illinois. Another example of a corona discharge treatment device for integration into an in-line production converter is Labeltec, available from Tantec A / S, Denmark. An example of a corona treatment device setup is to position the corona treatment head of the device at a specific height above the surface to be treated, with the head set at its maximum power setting (e.g., 30W). The height ranges from 3 mm to 30 mm and is related to the shape of the corona treatment head. Generally, the higher the position of the corona treatment head, the longer the treatment time required to achieve a certain level of hydrophilicity. A preferred distance between the corona treatment head and the surface to be treated at maximum power is 5 mm to 20 mm.
[0568] Corona discharge treatment creates hydrophilic regions in size and shape that generally correspond to the openings 513a1, 513a2 of mask 515, each with an invisible hydrophobic boundary, thereby enhancing the accuracy of reagent spotting. After corona discharge treatment, mask 515 is removed, and a wet reagent, typically in microliter (µl) volumes, is coated onto plastic layer 533, preferentially adhering to the hydrophilic regions corresponding to openings 513a1, 513a2, thus enhancing reagent placement accuracy. Compared to the untreated, relatively hydrophobic surface, the wet reagent spreads over a larger area on the hydrophilic surface, resulting in faster drying during manufacturing, and the dried reagent spots 511a1, 511a2, 511b1, 511b2 are better adhered to plastic layer 533. Drying time is highly dependent on spot volume, surface area, spot formulation, and drying technique. Lower spot volume, larger surface area, less in-situ sugar, higher temperature, and lower humidity will reduce drying time. The drying time can be as short as 1 to 2 minutes, preferably at a temperature below 40ºC. Because the reagent is spread uniformly on the hydrophilic region, the resulting dried reagent will rehydrate more rapidly when exposed to a liquid (such as an eluent containing the analyte). The reagent spot for each of reaction chambers 510a1, 510a2, 510b2, 510b2 is preferably a single spot that generally corresponds in size and shape to the openings 513a1, 513a2 of mask 515, but in some applications, the reagent spot may occupy multiple locations in one or more reaction chambers.
[0569] The dispensing volume depends on the concentration of the reagent and can range from 0.5 µl to 2.0 µl or more.
[0570] Before or after each laminated seal 532a is attached to the box body 502, a wet reagent may be applied to the hydrophilic area of the plastic layer 533.
[0571] After attaching the laminated seal 532a to the cartridge body 502, dispensing reagents onto the plastic layer 533 has the advantage of directly dispensing them to the region of interest without the need for additional treatment to ensure dispensing accuracy beforehand, which could jeopardize reagent performance or efficacy. A disadvantage of dispensing reagents after attaching the laminated seal 532a to the cartridge body 502 is that if reagent dispensing is defective, the entire cartridge must be discarded, which can be costly and wasteful. Similarly, due to the limited space within the cartridge, fitting the dispensing nozzle into the openings in the cartridge body 502 corresponding to the reaction chambers 510a1, 510a2, 510b1, and 510b2 can be difficult.
[0572] Spotting the reagent onto the plastic layer 533 before attaching the laminated seal 532a to the cartridge body 502 allows for higher spotting rates and fewer restrictions on fitting the dispensing nozzle in confined spaces. Defective dispensing costs are lower because the individual laminated seal 532a can be discarded instead of the entire cartridge. A disadvantage of spotting the reagent onto the plastic layer before attaching the laminated seal 532a to the cartridge body 502 is that the spot-shaped laminated seal 532a may need to be held and stored under controlled conditions that do not degrade or compromise the performance of the reagent spot before being attached to the cartridge. Additionally, the laminated seal needs to be physically disposed of, applied, and attached to the cartridge, which may damage or degrade the performance of the spot-shaped reagent.
[0573] Suitable devices for applying reagents during the spotting process include the iONE micro-dispensing instrument available from M2-Automation GmbH in Berlin, Germany, or the iZERO online production micro-dispensing instrument available from M2-Automation GmbH in Berlin, Germany.
[0574] As explained before and Figure 70 As shown, openings 513a1 and 513a2 can be made smaller than reaction / detection chambers 510a1, 510a2, 510b1, and 510b2, such that... Figure 8 As shown, separation may exist between the sides of reagent spots 511a1, 511a2, 511b1, 511b2 and the sides of the corresponding reaction chambers 510a1, 510a2, 510b1, 510b2. This helps ensure that reagents are not wicked into the area between the bottom surface 503 of the cartridge body 502 and the laminated seals 532a or 532b (whether during the initial spot formation process, if wet reagents are applied to the plastic layer 533 after the laminated seals are bonded to the cartridge body 502, or during the reaction process, when the dried reagent spots 511a1, 511a2, 511b1, 511b2 dissolve), making all reagents available for reaction within the reaction chambers.
[0575] In another example, the surface of plastic layer 533 can be treated with plasma to increase hydrophilicity. This disclosure covers other treatments that can effectively increase the hydrophilicity of the surface of plastic layers. Such treatments can include thermal oxidative chemical treatment (treatment at elevated temperatures with a mixture of chromic acid, sulfuric acid, and phosphoric acid for a short time), graft polymerization (surface activation followed by chemical grafting of hydrophilic chains), UV-ozone treatment (forming an oxide material on the surface and altering surface morphology and wettability), deposition of SiOx on polypropylene, and coating with surfactants. See, for example, Danu Ariono and Anita Kusuma Wardani, “Modification and Applications of Hydrophilic Polypropylene Films,” IOP Conference Series: Materials Science and Engineering; IOP Conf. Series: Materials Science and Engineering 214 (2017) 012014 ( https: / / iopscience.iop.org / article / 10.1088 / 1757-899X / 214 / 1 / 012014 / pdf ).
[0576] In another example, where the laminated seals 532a and 532b covering reaction chambers 510a1, 510a2, 510b1, and 510b2 are omitted and reaction chambers 510a1, 510a2, 510b1, and 510b2 are covered by a bottom film 530, reagent spots 511a1, 511a2, 511b1, and 511b2 (see [reference]) Figure 8 The reagent spot can be adhered to the bottom surface 503 of the bottom film 530 facing the box body 502 and the surfaces of the reaction chambers 510a1, 510a2, 510b1, 510b2 (for convenience, referred to as the top surface of the bottom film 530). In this example, the top surface of the bottom film 530 can be treated to increase the relative hydrophilicity of the portion of the top surface to which the reagent spot will adhere. Such treatment can include any treatment described herein, including corona discharge and plasma treatment. For treatments performed by corona discharge or plasma treatment, the top surface of the bottom film 530 can be masked (such as the one shown in the figure with...). Figure 70 The openings 513a1 and 513a2 are covered by a mask 515. When the masked film is treated by corona discharge or plasma, only the surface portion of the film exposed by the openings 513a1 and 513a2 is contacted by corona discharge or plasma, resulting in increased hydrophilicity only in those portions.
[0577] All other descriptions in this document regarding the composition, formation, size, etc. of reagent spots 511a1, 511a2, 511b1, 511b2 on the surface of the plastic layer 533 of the conductive laminates 532a, 532b, the materials used to form the mask, and the corona discharge parameters may be used for the reagent spots that are adhered to the top surface of the bottom film 530.
[0578] In alternative arrangements, if the surfaces of the laminated seal, the bottom film to be determined, or other types of materials enclosing the reaction chamber are already hydrophilic, it may be desirable to treat the surfaces to make portions of the surface hydrophobic, so that the speckled reagent will be attracted to only the hydrophilic portions of the surface. In this case, the surface can be used with those described herein and Figure 70 The mask 515 shown is an opposite mask covering, i.e., covering only (or more) portions of the surface to be spotted with the reagent, so that (or more) covered portions of the surface are left untreated and remain hydrophilic, while the remaining portions of the surface are treated to change their surface structure from hydrophilic to hydrophobic. Fabio Palumbo, Chiara Lo Porto, and Pietro Favia, "Plasma Nanotexturing of Polymers for Wetting Control: Why, What, and How," Coatings, 9, 640; October 3, 2019. https: / / www.mdpi.com / 2079-6412 / 9 / 10 / 640 This describes the process for producing hydrophobic polymer surfaces.
[0579] When laminated seals 532a and 532b are attached to the cartridge body 502, a retaining device can be used to ensure alignment of the speckled reagent on the plastic layer 533 with the reaction chambers 510a1, 510a2, 510b1, and 510b2. Laminated seals 532a and 532b can be supported in the retaining device, which may include alignment pins to align the cartridge body 502 with the laminated seals 532a and 532b. Laminated seals 532a and 532b can be carried on a backing liner including precision alignment features such as alignment pins and mating alignment holes, which precisely hold the laminated seals 532a and 532b in a known and controlled position on the retaining device. With the laminated seals 532a and 532b correctly aligned with the cartridge body, a heat-sealing head contacts the laminated seals 532a and 532b to heat-seal the laminated seals to the cartridge body, as described herein.
[0580] The laminated seals 532a and 532b are separated from the bottom film 530—that is, the laminated seals 532a and 532b are structurally and functionally isolated from the bottom film 530. Accordingly, depending on the specific operational, functional, and / or structural requirements (such as defined channels) for the bottom film, different formulations and configurations of the bottom film 530 can be employed without requiring changes to the laminated seals. In other examples, the bottom film covers a portion of the surface of the cartridge, which is spatially separated or isolated from one or more reaction / detection chambers covered by one or more laminated seals; in this case, cutouts formed in the bottom film are unnecessary.
[0581] The functional chambers W1 to W12 and SB of the cartridge body 502 contain or are configured to receive at least one of sample material, different reagent products, and purification columns during use of the fluid cartridge 500, as well as a fluid or solid intended for the preparation, amplification, and analysis of the sample. Other chambers may serve as mixing chambers to temporarily hold two or more different materials combined therein, or as waste chambers. Examples of the functions and / or contents contained in chambers W1 to W12 and CW are illustrated in Table 1 below:
[0582] Table 1
[0583] As explained above, chambers W1 to W5 and W7 to W10 each include through-holes H1 to H5 and H7 to H10 formed through the bottom wall of the respective chamber, and functional chamber W6 includes three through-holes H6, H11, and H12 formed through the bottom wall of the chamber. The syringe barrel SB includes central through-holes H1c, H2c, H3c, H4c, H5c, H6c, H7c, H8c, H9c, and H10c formed through the bottom wall of the barrel. Each of chambers W1 to W10 is in independent fluid communication with the central pool SB via channels formed by grooves G1, G2, G3, G4, G5, G6, G7, G8, G9, and G10, respectively, controlled by valves V1, V2, V3, V4, V5, V6, V7, V8, V9, and V10, and fluid can flow between these different functional chambers in one direction or the other (i.e., from each of chambers W1 to W10 to the syringe barrel SB or vice versa).
[0584] Details of the example of cap 516 are in Figures 15 to 17 As shown in the diagram. The cap 516 includes an upper portion having a radial wall 522 having a peripheral wall 520 extending axially around the radial wall 522. The cap 516 also includes a lower portion 519 defined by a peripheral wall 525 extending below the radial wall 522. The upper portion 518 of the cap 516 is wider than the lower portion 519, thus defining a radial annular shoulder 524. The peripheral wall 525 is inserted into the sample chamber W1; for this purpose, the wall 525 may be tapered, and the radial shoulder 524 contacts the top edge of the wall of the chamber W1. The lower portion 519 may also include radially extending annular ribs 526a, 526b projecting from the outer surface of the peripheral wall 525. A vent 523 is formed in the radial wall 522, and side vents 521a, 521b are formed in the peripheral wall 520.
[0585] Box 500 may include two functional sections. For example... Figure 6 and Figure 7As shown, the sample preparation section 504 of cartridge 500 includes multiple chambers (e.g., chambers W1 to W12) that contain or can receive various materials (which may include liquids or other fluids) used in sample preparation for performing assays or other procedures on the samples within the cartridge during operation of the cartridge by instrument 10. The sample preparation section 504 is configured to receive sample specimens in a sample chamber (e.g., chamber W1) (which may include or be connected to a fluid inlet port at which fluid samples are introduced into the sample chamber), and is configured to process the samples using materials contained in one or more other chambers within the sample preparation section 504, for example, to isolate target molecules (e.g., lysing and purifying nucleic acids using silica-based purification) from other components of the sample specimen, and is configured to combine the isolated molecules with materials used in performing assays (such as amplification reagents and / or detection probes) to form a reaction mixture. Amplification reagents and / or detection probes may be provided in a dried (e.g., lyophilized) form in one or more chambers W2 to W10 of the sample preparation section 504, and reconstruction fluids for combination and reconstruction with the reagents or probes may be contained in one or more chambers W2 to W10 of the sample preparation section 504. Valves V1 to V10, which control the flow of fluid into and out of chambers W1 to W10 respectively, and valves V11 and V12, which control the flow of fluid into and out of chamber W6, may be referred to as sample preparation (or processing) valves because they are located within chambers W1 to W10 of the sample preparation section 504 of the cartridge 500 and control the flow of fluid in chambers W1 to W10.
[0586] refer to Figure 6 and Figure 7 The reaction / detection section 506 of cartridge 500 is configured to receive a processed sample (reaction mixture) from the sample preparation section 504 and is configured to provide a platform for one or more reactions to occur, for example, to amplify and detect target molecules (e.g., real-time PCR). The reaction / detection section 506 includes one or more reaction chambers (e.g., reaction / detection chambers 510a1, 510a2, 510b1, 510b2), each of which defines a enclosure capable of containing a fluid substance, and within the enclosure, a reaction can occur, and a detectable signal emitted during the reaction can be detected from the enclosure. The detectable signal may be an optical signal (such as fluorescence), and the detection of the detectable signal can indicate the presence and / or amount of target molecules in the sample. Valves V13 to V18 that control the flow of fluid into and out of reaction chambers 510a1, 510a2, 510b1, and 510b2 can be referred to as reaction valves because they are located within reaction chambers 510a1, 510a2, 510b1, and 510b2 in the reaction / detection section 506 of housing 500 and control the flow of fluid into reaction chambers 510a1, 510a2, 510b1, and 510b2.
[0587] refer to Figure 9 and including detail A Figure 10 The protective vent 560 comprises two components: a vent membrane 562, which is hermetically sealed to the top of the cartridge body 502 to cover chambers W1 to W12 of the sample preparation section 504; and a protective cover 566, which is thermally laminated to the top surface of the vent membrane 562 and can be peeled off by the user from the vent membrane before use of the cartridge. A plunger orifice 563, formed at least in the vent membrane 562 (and optionally also provided in the protective cover 566), provides a passage to the cartridge body SB via a syringe plunger.
[0588] like Figure 10 As shown in detail A, the venting membrane 562 is a porous plastic membrane with two sets of orifices: through-holes 564 and blind-holes 565. The through-holes 564 extend completely through the thickness of the venting membrane, and the blind-holes 565 extend partially through the thickness of the membrane from the bottom surface of the venting membrane (the surface in contact with the housing body 502). The venting membrane allows gas / vapor to circulate via the through-holes and contains liquid within chambers W1 to W12 when the protective cover 566 is removed. When, for example, the membrane 562 is attached to the housing body 565, the blind-holes 565 enhance the adhesion of the membrane 562 to the housing body 502 because the plastic of the housing body melts into the blind-holes 565.
[0589] In one example, the protective cover 566 comprises a three-layer aluminum laminate: polyester (PET) / aluminum / polyethylene (PE), and is heat-laminated onto the top (exposed) surface of the venting membrane 562. The protective cover 566 may include a pull tab 567 extending beyond the venting membrane to allow a user to grip the cover and peel it off from the membrane. The PE layer of the protective cover 566 melts during the heat lamination process and partially flows into the venting membrane through orifices 564 to limit or prevent the evaporation of liquid stored in one or more of the chambers W1 to W12 of the fluid cartridge 500 during the manufacture, storage, and transport of the cartridge while the protective cover 566 is in place. When the protective cover 566 is peeled off from the venting membrane 562 before use of the cartridge 500, the through-holes 564 of the venting membrane 562 are released from the PE, and all PE “filaments” clogging the through-holes 564 are removed, leaving the aluminum laminate attached to the protective cover 566. In one embodiment, the protective vent 560 does not cover chamber W1 (sample chamber) and may have an opening formed at the location of chamber W1 to allow access to the sample chamber when the protective vent is attached to the box.
[0590] Box 500 includes a pump mechanism for moving between the pool and the chamber and for moving fluid through grooves / channels and through-holes. Figure 3In the embodiment shown, the pump mechanism includes an injection barrel defined by an elastomeric stop 540 disposed within the injection barrel body SB and actuated by the injection barrel plunger 362 of the instrument 10, as described below. Raising the stop 540 within the injection barrel body SB creates a vacuum within the injection barrel body SB, which draws fluid through channels G1 to G10 and orifices H1c to H10c into the injection barrel body SB. Valves V1 to V10 can be actuated to control which one or more of channels G1 to G10 are open to the injection barrel body SB. Typically, all valves except one of V1 to V10 will be closed, allowing fluid to be drawn into the injection barrel body SB through one of the channels G1 to G10 and orifices H1c to H10c.
[0591] The stop 540 within the syringe barrel SB generates pressure within the syringe barrel, which forces fluid out of the syringe barrel SB through orifices H1c to H10c and channels G1 to G10. Similarly, valves V1 to V10 can be actuated to control which channels(s) are open to the syringe barrel SB. Typically, all valves except one of V1 to V10 will be closed, causing fluid to be forced out of the syringe barrel SB through orifices H1c to H10c and one of the associated channels G1 to G10.
[0592] like Figure 11 As can be seen, the stop 540 is generally cylindrical and has a diameter that forms a sliding fit with the cylindrical wall 508 of the syringe body SB. The stop 540 may include one or more peripheral rings (e.g., rings 542, 544) to facilitate sealing contact between the stop 540 and the inner surface of the cylindrical wall 508.
[0593] like Figure 18 and Figure 19 As shown, the stop 540 includes: a plunger recess 546 for receiving a plunger head 364 at the end of the syringe plunger 362, and a plunger seat 548 for releasably retaining the plunger head 364 of the syringe plunger 362, as described below. The plunger recess 546 may include a conical (chamfered) portion to help guide the plunger head 364 of the syringe plunger into the plunger seat 548.
[0594] During the transport and storage of cartridge 500, and before plunger 362 engages stop 540, stop 540 is retained within syringe barrel SB and presses against the bottom wall of syringe barrel SB by a blocking mechanism, thereby blocking orifices H1c to H10c. Figure 11As shown, the blocking mechanism may include a blocking ring 550 fixed to the top edge of the cylindrical wall 508 of the syringe barrel SB, and a blocking member 570 is configured to engage with the blocking ring 550 and to disengage from the blocking ring 550 when the plunger 362, which is engaged with the stop member 540, is moved downward through the blocking member 570.
[0595] The blocking ring 550 includes an annular edge 552 and an axial ring 556 extending from the outer periphery of the annular edge 552. The bottom side of the annular edge 552 contacts the top circular edge of the cylindrical wall 508 of the syringe barrel SB. The inner diameter of the axial ring 556 is preferably only slightly larger than the outer diameter of the cylindrical wall 508, such that there is almost no lateral clearance between the blocking ring 550 and the cylindrical wall 508. The inner diameter of the annular edge 552 is preferably smaller than the inner diameter of the cylindrical wall 508 (and smaller than the diameter of the stop 540), such that the blocking ring 550 prevents the stop 540 from being removed from the syringe barrel SB. A radial notch 554 is formed across the top of the annular wall 552. The blocking ring 550 includes three radially extending flanges or tabs 558a, 558b, and 558c that project outwardly from the bottom edge of the axial ring 556 at an angle.
[0596] The blocking ring 550 is fixed to the top of the cylindrical wall 508, for example, by adhesive, thermal welding or ultrasonic welding, or the blocking ring and the cylindrical wall can be integrally formed as a single piece.
[0597] like Figures 11 to 14 As shown, the blocking member 570 includes a cap portion 572 and a central tube 586. The cap portion 572 includes a top first cap portion 574 and a lower second cap portion 582, the lower second cap portion being coaxial with the first cap portion 574 and having a larger outer diameter than the first cap portion. The first cap portion 574 is defined by a top radially oriented wall 576 and a side axially oriented wall 575. The side wall 575 has an inner diameter slightly larger than the outer diameter of the axial ring 556 of the blocking member ring 550, such that the first cap portion 574 of the blocking member 570 fits onto the blocking member ring 550 with virtually no lateral clearance between the first cap portion 574 of the blocking member 570 and the blocking member ring 550. The second part 582 is defined by a lateral axial wall 583 having an inner diameter larger than the outer diameter of the circular part of the outer edge of the flanges 558a, 558b, 558c of the outer blocking ring 550, such that the second cap portion 582 of the blocking member 570 fits over and passes through the flanges 558a, 558b, 558c of the blocking member 550.
[0598] The blocking member 570 includes three angled flanges 584a, 584b, and 584c projecting inwardly from the lower edge of the axial wall 583 of the second cap portion 582 of the cap portion 572. The distance between the top surface of each radial flange 584a, 584b, and 584c and the bottom surface of the radial wall 576 of the first cap portion 574 is at least as large as the distance between the bottom surface of each flange 558a, 558b, and 558c of the blocking member ring 550 and the top surface of the annular edge 552 of the blocking member ring 550. Accordingly, when the blocking member 570 is placed on the blocking member ring 550, wherein the top surface of the annular edge 552 of the blocking member ring 550 contacts the bottom surface of the radial wall 576 of the blocking member 570, the blocking member 570 can be rotated relative to the blocking member ring 550 to place each of the flanges 584a, 584b, 584c of the blocking member 570 below the corresponding one of the flanges 558a, 558b, 558c of the blocking member ring 550, thereby releasably interlocking the blocking member 570 and the blocking member ring 550.
[0599] The central tube 586 extends below the top wall 576 of the first cap portion 574 of the cap portion 572. When the stop 540 contacts the bottom wall of the syringe barrel SB, the length of the central tube 586 is greater than the distance from the top of the stop to the top wall of the annular edge 552 of the blocking ring 550. Accordingly, the central tube 586 must be pushed downwards to partially compress the stop 540 so that the bottom surface of the top wall 576 of the first cap portion 574 can contact the top of the annular edge 552 of the blocking ring 550. This compression of the stop provides a seal to block the through holes H1c to H10c in the syringe barrel SB. Furthermore, the elasticity of the stop 540 pushes the central tube 586 upward, thereby causing the flanges 584a, 584b, and 584c of the blocking member 570 to push upward against the flanges 558a, 558b, and 558c of the blocking ring 550. This increases the friction between the flanges 584a, 584b, and 584c and the flanges 558a, 558b, and 558c, thus retaining the blocking member 570 in a fixed position relative to the blocking ring 550. The retained blocking member 570 holds the stop 540 in a compressed state against the bottom wall of the injection barrel SB.
[0600] The top wall 576 of the first cap portion 574 includes a central opening. A central tube 586 extends downward from the perimeter of the central opening from the top wall 576. The central tube 586 includes opposing cam walls 588a, 588b extending downward from opposite sides of the central opening formed in the top wall 576. Each cam wall 588a, 588b includes associated cam edges 590a, 590b having a helical curve extending from the top wall 576 along one side of each cam wall 588a, 588b to an end ring 592, the end rings extending continuously around the circumference of the lower end of the central tube 586.
[0601] Radial gaps 577a and 577b are formed on opposite sides of the central opening of the top wall 576 and are arranged between the cam walls 588a and 588b. Therefore, the radius 578a from the center of the opening to each cam wall 588a and 588b (i.e., the diameter between the opposite walls 588a and 588b) is smaller than the radius 578b from the center of the opening to the outer edge of each gap 577a and 577b (i.e., the diameter between the opposite gaps 577a and 577b).
[0602] The first cap portion 574 of the cap portion 572 of the plug 570 includes angled cutouts 580a, 580b, 580c formed in the axially oriented sidewall 575 to facilitate the molding of internal features such as flanges 584a, 584b, 584c.
[0603] Instrument 10 includes a heat / detector mechanism that may include components or subsystems of instrument 10 and operates to heat or cool reaction / detection chambers 510a1, 510a2, 510b1, 510b2 and, when cartridge 500 is inside instrument 10, to detect optical signals emitted by reactions occurring within reaction / detection chambers 510a1, 510a2, 510b1, 510b2. Figure 23 and Figure 24 This is a partial top perspective view of the lower rack 400, showing the box support frame 402 with and without the box 500. Figure 23 A box support frame 402 is shown, including a box support bracket 404 on which the box can be operatively supported. Figure 24 The box support frame 402 of the support box 500 is shown. Figure 23A This is a perspective view of an isolated box support bracket 404. The box support bracket 404 may include a pad 403 made of an elastic material (such as rubber) that is fixed to a platform 405 of a box support frame 402. Figure 23A As shown, instrument 10 may include a plurality of valve actuator heads 406a to 406r formed in a gasket 403. Figure 23AThe example shown contains eighteen actuator heads, each of which, 406a to 406r, is associated with one of the valves V1 to V18 of the housing 500. Each actuator head 406a to 406r includes a recess (which may be as follows) Figure 23A (as shown in the diagram, circular), the recess has a protrusion centered within the recess and projecting above the bottom of the recess. An actuator piston or rod is associated with each actuator head 406a to 406r. Each actuator piston is arranged below the liner 403 and oriented generally perpendicular to the surface of the cartridge support bracket 404, wherein the tip of the piston extends into the underside of the protrusion of the actuator head. Each actuator piston is selectively actuated—as described herein—to move between a first position and a second position, in which the top of the protrusion of the actuator head 406a to 406r is flush with or recessed relative to the top surface of the liner 403, and in the second position, the top of the protrusion of the associated actuator head 406a to 406r is pushed above the top surface of the liner 403. When in the second protruding position, the valve actuator heads 406a to 406r associated with each valve V1 to V18 of the cartridge 500 (see...) Figure 7 By selectively closing the associated valve by pressing the protrusion upwards, this will cause the deformable bottom membrane 530 of the box (see...) Figure 8 Press it into contact with the valve seat.
[0604] The box support bracket 404 is supported on the box support frame 402 of the lower frame 400, attached to the box support frame, or an integral part of the box support frame, and the box support frame 402 is supported on the base plate 408, attached to the base plate, or an integral part of the base plate.
[0605] Instrument 10 includes a movable holder that supports a test platform (such as a housing 500) and is selectively laterally movable relative to other parts of the instrument between a position in which the holder extends from instrument 10 such that the housing 500 or other test platform can be placed into or removed from the holder, and an operational position in which the housing 500 supported on the holder is moved into the instrument, in which the test platform, or a portion thereof, is positioned between a first heater and a second heater, as will be described below. Figure 23 As shown, the movable frame 414 encompasses a box support frame 402 and a box support bracket 404. Frame 414 includes tracks 416a and 416b, which are held together by crossbars 426 extending between the ends of tracks 416a and 416b in a spaced-apart arrangement. The tracks 416a and 416b... Figure 23 The invisible opposite end is separated by another transverse piece 428 (see Figure 1 and Figure 2 The tracks 416a and 416b are arranged at intervals, such that they are generally parallel to each other. The frame 414 is positioned relative to the box support frame 402, the box support bracket 404, and the base plate 408. Figure 23 The retraction position shown in the image is moved to... Figure 23 The extended position to the right of the position shown in the diagram. Instrument 10 includes actuators for automating (e.g., motorizing) movement of frame 414 relative to box support frame 402 and box support bracket 404. In one example, track 416b includes rack 418, and a motor (not shown) includes a drive shaft and gear (not shown) engaging rack 418 to achieve powered movement of frame 414 between the extended and retracted positions as the motor rotates the drive shaft and gear in one or the other direction.
[0606] refer to Figure 1 and Figure 2 The box holder 412 is supported on the frame 414 and moves laterally between an extended and a retracted position. The box 500 is supported within the box holder 412 on a short lateral flange that extends below the box 500 along the opposite side of the box and, when the box holder 412 and the frame 414 are in the retracted position to hold the box 500 above the box support bracket 404, the short lateral flange does not overlap with or otherwise interfere with the box support bracket 404. The box holder 412 is supported relative to the frame 414 by a spring 417 (see [link to spring 412]). Figure 23 (Only one spring is shown) supports, the springs being arranged in recesses 415a, 415b respectively formed in the tops of tracks 416a, 416b (see... Figure 23A spring is positioned between the retainer 412 and the tracks 416a, 416b to hold the retainer 412 in an elevated position above the tracks 416a, 416b, such that when the frame 414 moves between an extended position and a retracted position, the box 500 carried on the box retainer 412 can move above the box support bracket 404 without contacting the box support bracket 404. When the frame 414 and the box support retainer 412 retract to position the box 500 carried on the retainer 412 above the box support bracket 404, and a downward force is applied to the top of the box 500 (as described below), the spring between the box retainer 412 and the tracks 416a, 416b will allow the box 500 and the retainer 412 to deflect downwards, and position the box 500 supported by the retainer 412 in contact with the box support bracket 404. When the downward force is removed, the spring will again lift the retainer 412 and the box 500 above the frame 414 and the box support bracket 404, so that the frame 414, retainer 412 and box 500 can move freely relative to the box support bracket 404 without contacting the box support bracket 404.
[0607] Instrument 10 may further include sensors 422, 424 for detecting when the retainer 412 and frame 414 are in an extended or retracted position. In one example, each sensor includes an optical sensor with an optical transmitter and an optical receiver. The transmitter emits a light beam that is blocked by rails 416a or 416b from reaching the receiver until rails 416a or 416b are positioned at a notch or opening formed in the corresponding rail, allowing the beam from the sensor transmitter to be received by the sensor receiver. For example, as Figure 23 As shown, sensor 424 can be a holder extension sensor. For this holder extension sensor, the beam from the sensor transmitter is blocked by track 416b until frame 414 is in the extended position and a notch formed in track 416b aligns with the transmitter and receiver of sensor 424, such that the beam from the transmitter is received by the receiver. The resulting signal generated by sensor 424 then indicates that frame 414 and holder 412 are in the extended position. Similarly, sensor 422 can be a holder retraction sensor. For this holder retraction sensor, the beam from the sensor transmitter is blocked by track 416a until frame 414 and holder 412 are in the retracted position and a notch formed in track 416a aligns with the transmitter and receiver of sensor 422, such that the beam from the transmitter is received by the receiver. The resulting signal generated by sensor 422 then indicates that frame 414 and holder 412 are in the retracted position.
[0608] refer to Figures 27 to 29The upper frame 300 includes an upper block 302 and a motor mounting component 314. The motor mounting component includes side supports 306a and 306b, a top crossbar 308 extending between the side supports 306a and 306b (but not necessarily between the top ends of the side supports 306a and 306b), and an intermediate crossbar 310 extending between the side supports 306a and 306b at a spaced-apart position below the top crossbar 308. The lower ends 312a and 312b of the side supports 306a and 306b are respectively attached to the base plate 408 of the lower frame 400 at position 410 (see...). Figure 23 and Figure 24 The pressure plate 320, made of, for example, molded plastic or a similar material (e.g., Delrin), is attached to the bottom side of the upper block 302 by means of a spring mount 322 (see [link]). Figure 28 In one example, there are four spring mounts 322 between the pressure plate 320 and the upper block 302; two spring mounts 322 are located at... Figure 28 As can be seen, the spring mount is a connector (e.g., bolt or rod) between the pressure plate 320 and the upper block 302, creating a gap between them, and a spring (e.g., a helical compression spring) is arranged within the gap, such that the pressure plate 320 and the upper block 302 are held separately. The upper block 302 is configured for automated (e.g., motorized) movement relative to the base plate 408 of the lower frame 400, as will be described below, until the pressure plate 320 abuts against the top portion of the cassette 500 supported on the cassette support bracket 404 (e.g., the top portion of the sample preparation section 504 of the cassette 500 placed within the instrument 10), and the pressure plate 320 is capable of deflecting relative to the upper block 302 when sufficient force is applied to overcome the spring force of the spring mount 322.
[0609] Valve actuator
[0610] Instrument 10 includes one or more valve actuators, which include valve actuator pistons or simply actuator pistons for selectively actuating one of actuator heads 406a to 406r to open one of valves V1 to V18 associated with the actuator head and allow fluid flow within the cartridge through the associated valve. In one example, actuator heads 406a to 406r are associated with valves V1 to V18 respectively, and each actuator piston operably engaged with each actuator 406a to 406r is biased in an extended (first) position such that when cartridge 500 is placed into instrument 10 and pressure plate 320 is lowered onto the cartridge, each actuator piston presses against a protrusion of its associated actuator head 406a to 406r to operably engage the associated valve by pressing against it to close the valve. Therefore, when the box is placed in the box support bracket 404 and the frame 414 moves from its extended position to its retracted position, all valves V1-V18 are initially closed because the associated actuator pistons of actuator heads 406a to 406r are biased in the extended position to push the actuator heads into the extended position and move the valves into the closed position. To open any of the valves, the associated actuator pistons and actuator heads 406a to 406r retract to their second position over the biasing force disengaging from the associated valve, thereby opening the valve. The valve actuator of instrument 10 is configured and controlled to selectively retract at least one actuator piston to open the valve associated with the retracted piston. The biasing force extending the actuator piston into the extended position can be generated by components of the valve actuator.
[0611] In one example, the valve actuator includes one or more piston actuator mechanisms, wherein the piston actuator mechanisms are coupled to or otherwise selectively engaged with each valve actuator piston such that, as the piston actuator mechanism moves, it applies a force to the valve actuator piston coupled to or engaged by the piston actuator mechanism to overcome biasing forces and move the actuator piston from its first position to its second position, thereby opening the valve associated with the actuator piston. Continued movement of the piston actuator mechanism removes the force applied to the actuator piston coupled to it, or disengages the piston actuator mechanism from the actuator piston, thereby removing the force applied to the actuator piston to allow it to move back to its first position under biasing forces to close the valve associated with it.
[0612] In another example, the valve of the box can be configured such that the valve is opened by pushing the valve with the associated valve actuator head and valve actuator piston, and the valve is closed by releasing the pushing force applied by the associated valve actuator head and valve actuator piston. In this case, in their first biased position, the valve actuator piston engages the associated valve to position the valve in the open position, and each valve actuator piston selectively retracts from its first position to its second position against the bias force, changing the associated piston from the open position to the closed position.
[0613] like Figure 1 As shown, instrument 10 includes a first valve actuator 1300 for selectively retracting an actuator piston associated with one of actuator heads 406a to 406l and one of sample preparation (or treatment) valves V1 to V12 arranged in a circular pattern around the syringe barrel SB within the sample preparation section 504 of cartridge 500, and associated with one of the chambers H1 to H12 of pools W1 to W10 (see [link to documentation]). Figure 4 and Figure 5 ).like Figure 1 and Figure 2 As shown, the instrument 10 further includes a second valve actuator 740 for selectively retracting one or more actuator pistons associated with any one of the reaction valves V13 to V18 of the reaction chambers 510a1, 510a2, 510b1, and 510b2 of the cartridge 500 within the reaction / detection section 506 of the actuator heads 406m to 406r and the cartridge 500 (see [link to instrument 10]). Figure 4 and Figure 5 ).
[0614] like Figure 47 and Figure 49 As shown, the first valve actuator 1300 includes a rotary valve actuator having a housing 1302 defined by a lower housing 1304 and an upper housing 1306 connected to each other, for example by suitable fasteners, a plurality of valve actuator pistons 1320 extending upward through a guide slot 1308 formed in the top surface of the upper housing 1306, and a rotary actuator motor 1312 supported on a motor mount 1310.
[0615] like Figure 52As shown, each valve actuator piston 1320 includes a contact rod 1322. The contact rod 1322 of each valve actuator piston 1320 extends into an associated opening formed through the platform 405 of the housing support frame 402 and engages a protrusion of one of the actuator heads 406a to 406l formed in the liner 403 of the housing support bracket 404. Each valve actuator piston 1320 may further include a stop flange 1324 to prevent over-insertion of the valve actuator piston 1320 into the platform 405; a cam block 1326 having a cam follower surface 1328, which, in the shown embodiment, has an inverted "V" shape; a lower rod 1330 projecting directly below the cam block 1326; and a spring rod 1332 projecting below the lower rod 1330. Figure 48 and Figure 50 As shown, the lower rod 1330 and spring rod 1332 of the valve actuator piston 1320 extend into the housing 1302. Figure 49 As shown, the guide slots 1308 formed in the top surface of the upper housing 1306 have a shape conforming to the shape of the lower rod 1330. In the illustrated embodiment, the lower rod 1330 has a "T"-shaped cross-section, and each guide slot 1308 has a conforming shape that allows each piston 1320 to move axially up and down within its associated guide slot 1308 while preventing each piston from rotating about its longitudinal axis. Each valve actuator piston 1320 includes an associated spring 1334, which is coaxially arranged above the spring rod 1332 and seated within the lower housing 1304 to apply an upward biasing force to the associated valve actuator piston 1320.
[0616] like Figure 49 and Figure 50 As shown, the valve actuator piston 1320 is arranged in a circular configuration, with the cam follower surface 1328 of the valve actuator piston 1320 facing the center of the circular configuration. The cam block 1326 of each valve actuator piston 1320 may have a truncated pie shape to facilitate the circular arrangement of the piston 1320. Each valve actuator piston 1320 is operatively associated with one of the associated valves V1 to V12 via actuator heads 406a to 406l, and is movable between a first position corresponding to a closed configuration of the associated valve and a second position corresponding to an open position of the associated valve.
[0617] like Figure 48 and Figure 50As shown, the rotary valve actuator 1300 includes a cam rotor 1336 rotatably supported by an upper bearing 1364 and a lower bearing 1368 for rotation about a cam rotor rotation axis 1339. The cam rotor 1336 includes a vertically oriented central shaft 1338 having a longitudinal axis defining the rotation axis 1339 and a rotor head 1340 at its apex. The rotor head 1340 has a cup-shaped structure including a radially extending flange 1342 and a circular axial wall 1344 coaxially arranged relative to the rotation axis 1339. The end 1348 of the central shaft 1338, disposed inside the axial wall 1344, is supported in the upper bearing 1364.
[0618] The cam rotor 1336 is connected to the rotary actuator motor 1312 to achieve powered rotation of the cam rotor 1336. In one example, the cam rotor 1336 is connected to the motor 1312 via a drive gear 1314 mounted on the drive shaft of the motor 1312, a transmission gear 1316, and a cam rotor gear 1318 fixed to the end of the central shaft 1338 of the cam rotor 1336.
[0619] like Figure 48 and Figure 51 As shown, the rotary valve actuator 1300 further includes a rotary cam 1358 extending radially from the rotor head 1340, and includes a cam rod 1360 extending radially from the rotor head 1340 and a cam roller (e.g., roller bearing) 1362 fixed to the cam rod 1360 and rotatable about the longitudinal axis of the cam rod 1360 to engage a cam follower surface 1328 of the valve actuator piston 1320.
[0620] The rotary cam 1358 is configured such that the cam roller 1362 is positioned at the same radial distance from the axis of rotation 1339 of the cam rotor 1336 and the cam follower surface 1328 of the circularly arranged valve actuator piston 1320. As the cam rotor 1336 rotates about its axis of rotation 1339, the cam roller 1362 of the rotary cam 1358 is configured to sequentially engage the cam follower surfaces 1328 of the valve actuator piston 1320. The cam rod 1360 and the valve actuator piston 1322 are positioned such that the longitudinal axis of the cam rod 1360 is at or near its bottom edge 1327 and below the tip 1329 of the cam follower surface 1328. As the cam rotor 1336 and the rotary cam 1358 rotate about the rotation axis 1339, the cam roller 1362 rolls along the cam follower surface 1328 from the bottom edge 1327 toward the tip 1329, and the angle of the cam follower surface 1328 causes the valve actuator piston 1320 to be pushed downward by the action of the cam roller 1362 of the rotary cam 1358, moving the valve actuator piston 1320 from its spring-biased first (valve closed) position to its second (valve open) position, thereby releasing (opening) the associated valve engaged with the contact rod 1322 of the valve actuator piston 1320. As the cam rotor 1336 and the rotary cam 1358 continue to rotate, the cam roller 1362 rolls downward from the tip 1329, and the spring 1334 pushes the valve actuator piston 1320 upward so that the contact rod 1322 closes the associated valve again.
[0621] The top tip 1329 of the cam follower surface 1328 may be flat or otherwise shaped to provide a stable rest position for the cam roller 1362 when the cam roller 1362 holds the valve actuator piston 1320 in the downward position.
[0622] Rotational positioning and control of the cam rotor 1336 can be provided by a rotary position sensor, which in the illustrated example includes an optical sensor 1350 comprising an optical transmitter and an optical receiver, attached to a printed circuit board 1356 and positioned and configured to detect the passage of sensor markers 1346 arranged along the top edge of the axial wall 1344 of the rotor head 1340. Each sensor marker 1346—or the gap between consecutive sensor markers 1346—can correspond to the position of one of the actuator pistons 1320, such that a signal generated by the sensor 1350 when a marker or gap is detected indicates the rotational position of one of the actuator pistons 1320. The first valve actuator 1300 and / or instrument 10 may include other control features, such as a rotary encoder (not shown) coupled to the rotary actuator motor 1312, to facilitate precise positioning of the rotary cam 1358, thereby precisely controlling which of the valves V1 to V12 is opened, thus enabling fluid to move in an orderly manner to and / or from the sample cell W1 and the functional chamber W21 and the syringe barrel SB to prepare the processed sample.
[0623] like Figure 53 As shown, the second valve actuator 740 includes a frame 742 having a bottom wall 744, an end wall 748, a first side 750, and a second side 754. A plurality of valve actuator pistons 900a, 900b, 900c, 900d, 900e, and 900f (six valve actuator pistons in the illustrated example) extend upward from associated piston openings formed in the bottom wall 744 of the frame 742. Each of the valve actuator pistons 900a to 900f is operatively associated with one of valves V13, V14, V15, V16, V17, and V18 via actuator heads 406m to 406r, and is movable between a first position corresponding to a closed configuration of the associated valve and a second position corresponding to an open position of the associated valve.
[0624] In alternative examples, the valve actuator may have fewer or more than six valve actuator pistons. An example of a valve actuator with eight valve actuator pistons is described below.
[0625] The first motor 758, the second motor 760, and the third motor 762 can be mounted to the end wall 748 of the frame 742. Each of the motors 758, 760, and 762 can be a stepper motor. The second valve actuator 740 includes a first camshaft 1000, a second camshaft 1012, and a third camshaft 1024. The first motor 758 is coupled to the first camshaft 1000 to achieve rotation of the first camshaft 1000 about a first camshaft rotation axis 1001 corresponding to the longitudinal axis of the first camshaft 1000 (see [link to relevant documentation]). Figure 54The second valve actuator 740 may include an encoder or other sensor mechanism that is coupled to or otherwise operable with the first motor 758 and communicates with the controller for detecting and controlling the rotational position of the first camshaft 1000. The second motor 760 is coupled to the second camshaft 1012 for realizing the rotation of the second camshaft 1012 about a second camshaft rotation axis 1013 that corresponds to the longitudinal axis of the second camshaft 1012 and is parallel to the rotation axis 1001 of the first camshaft (see...). Figure 54 The second valve actuator 740 may include an encoder or other sensor mechanism that is coupled to or otherwise operable with the second motor 760 and communicates with the controller to detect and control the rotational position of the second camshaft 1012. The third motor 762 is coupled to the third camshaft 1024 to realize the third camshaft 1024 about a third camshaft rotation axis 1025 that corresponds to the longitudinal axis of the third camshaft 1024 and is parallel to the rotation axis 1001 of the first camshaft and the rotation axis 1013 of the second camshaft (see...). Figure 54 The second valve actuator 740 may include an encoder or other sensor mechanism that is coupled to or otherwise operable with the third motor 762 and communicates with the controller for detecting and controlling the rotational position of the third camshaft 1024.
[0626] like Figure 54 As shown, the journal end 1006 of the first camshaft 1000, opposite the first motor 758, is rotatably supported by a first bearing mount 764. Figure 53 As shown, the first bearing mount 764 includes a mounting block 766 fixed to the bottom wall 744 of the frame 742, an upright support 768 extending upward from the end of the mounting block 766, and a bearing 770 disposed in the upper end of the support 768, the upper end receiving the journal end 1006 of the first camshaft 1000. Figure 54 As shown, the journal end 1018 of the second camshaft 1012, opposite to the second motor 760, is rotatably supported by the second bearing mount 772. Figure 53 As shown, the first bearing mount 772 includes a mounting block 774 fixed to the bottom wall 744 of the frame 742, an upright support 776 extending upward from the end of the mounting block 774, and a bearing 778 disposed in the upper end of the support 776, the upper end receiving the journal end 1018 of the second camshaft 1012. Figure 54As shown in the figure, the journal end 1028 of the third camshaft 1024, opposite the third motor 762, is rotatably supported by the third bearing mount 780. Although not fully shown in the figure (see Figure 1028), the journal end 1028 of the third camshaft 1024 is rotatably supported by the third bearing mount 780. Figure 53 However, the third bearing mount 780 has a similar shape factor to the first bearing mount 764 and the second bearing mount 772, including a mounting block fixed to the bottom wall 744 of the frame 742 (in Figure 53 (Not visible in the middle) An upright support 784 extending upward from the mounting block, and a bearing 786 arranged in the upper end of the support, the upper end receiving the journal end 1028 of the third camshaft 1024.
[0627] refer to Figure 54 The first camshaft 1000 includes a first camless portion 1002 that is radially symmetrical with respect to the first camshaft rotation axis 1001, a first cam lob 1008 that is radially asymmetrical with respect to the first camshaft rotation axis 1001, a second camless portion 1004 that is radially symmetrical with respect to the first camshaft rotation axis 1001, a second cam lob 1010 that is radially asymmetrical with respect to the first camshaft rotation axis 1001, and a journal end 1006. The second camshaft 1012 includes a first camless portion 1014 that is radially symmetrical with respect to the second camshaft rotation axis 1013, a first cam lob 1020 that is radially asymmetrical with respect to the second camshaft rotation axis 1013, a second camless portion 1016 that is radially symmetrical with respect to the second camshaft rotation axis 1013, a second cam lob 1022 that is radially asymmetrical with respect to the second camshaft rotation axis 1013, and a journal end 1018. The third camshaft 1024 includes a radially symmetrical, non-convex portion 1026 with respect to the third camshaft rotation axis 1025, a radially asymmetrical first cam convex angle 1030 with respect to the third camshaft rotation axis 1025, a radially asymmetrical second cam convex angle 1032 with respect to the third camshaft rotation axis 1025, and a journal end 1028.
[0628] refer to Figure 59 and Figure 60The diagram illustrates a single valve actuator piston 900 (valve actuator pistons 900a to 900f are identical or substantially identical in form factor), each of which includes a contact rod 902, a peripheral rib 904 (optionally) surrounding the contact rod 902, an extension 906 (whose width (or diameter if the extension 906 is cylindrical) may be larger than the contact rod 902), a lever collar 908 (arranged at the bottom end of the extension 906 and having a width (e.g., diameter) smaller than the width (e.g., diameter) of the extension 906), and a spring housing 910. The contact rod 902 of each valve actuator piston 900a to 900f extends into an associated opening formed through a platform 405 of a housing support frame 402 and engages a protrusion formed in a pad 403 of a actuator head 406m to 406r in the housing support bracket 404. The peripheral rib 904 may have a width slightly smaller than the width of the opening formed in the platform 405 (e.g., the diameter if the contact rod 902 is cylindrical) to allow the contact rod 902 to move back and forth within the opening. Furthermore, the rib 904 provides minimal edge contact between the contact rod 902 and the inner wall of the opening in the platform 405 to reduce the likelihood of the contact rod 902 engaging within the opening.
[0629] The length of the extension 906 (which may be elongated as shown) provides the necessary clearance between the second valve actuator 740 and the housing support frame 402, and the increased width of the extension 906 provides increased rigidity to reduce or prevent bending or buckling of the valve actuator piston 900.
[0630] The valve actuator piston 900 includes a lateral flange defining a lever seat 912, which is engaged by an associated actuator lever to lower the valve actuator piston 900, as will be described herein. In one example, the lever seat 912 is defined by the top of a lever collar 908 and a spring housing 910 (having a width (e.g., diameter) larger than the width of the lever collar 908).
[0631] Figure 56 Actuator pistons 900a and 900b are shown respectively arranged within piston openings 746a and 746b formed in the bottom wall 744, and Figure 57 Actuator pistons 900c, 900d, 900e, and 900f are shown, respectively, arranged within piston openings 746c, 746d, 746e, and 746f formed in the bottom wall 744. (See diagram for reference.) Figure 56 and Figure 57As shown, the spring housing 910 includes a hollow cylindrical chamber 914 that receives a spring 916, the spring abutting against a base plate 745 covering the bottom ends of openings 746a to 746f formed in the bottom wall 744, to axially bias the valve actuator piston 900 axially upward in its longitudinal direction to a first position of the valve actuator piston 900. (See again) Figure 59 and Figure 60 The lower portion 911 of the spring housing 910 may have a width (e.g., diameter) smaller than the width (e.g., diameter) of the upper portion 913 of the spring housing 910, and the lower end of the spring housing 910 may have a radial rib 915, the radial rib having a width (e.g., diameter) slightly smaller than the width of the piston opening 746, so as to allow the lower end of the spring housing 910 to move back and forth within the piston opening 746. Furthermore, the rib 915 provides minimal edge contact between the spring housing 910 and the inner wall of the piston opening 746, so as to reduce the likelihood of the spring housing 910 engaging within the piston opening 746.
[0632] In the configuration of the second valve actuator 740 shown, valve actuator piston 900a is associated with actuator head 406m of valve V13 (i.e., open and closed), valve actuator piston 900b is associated with actuator head 406n of valve V14 (i.e., open and closed), valve actuator piston 900c is associated with actuator head 406o of valve V15 (i.e., open and closed), valve actuator piston 900d is associated with actuator head 406p of valve V16 (i.e., open and closed), valve actuator piston 900e is associated with actuator head 406q of valve V17 (i.e., open and closed), and valve actuator piston 900f is associated with actuator head 406r of valve V18 (i.e., open and closed).
[0633] Reference Figure 54 The second valve actuator 740 further includes a first pivot actuator lever 920 operatively engaged by a first camshaft 1000, a second pivot actuator lever 930 operatively engaged by a third camshaft 1024, a third pivot actuator lever 940 operatively engaged by the first camshaft 1000, a fourth pivot actuator lever 950 operatively engaged by a second camshaft 1012, a fifth pivot actuator lever 960 operatively engaged by the second camshaft 1012, and a sixth pivot actuator lever 970 operatively engaged by the third camshaft 1024.
[0634] Each valve actuator piston 900a to 900f is associated with one of actuator levers 920, 930, 940, 950, 960, 970 to connect the valve actuator piston to one of camshafts 1000, 1012, or 1024. For example... Figure 53 , Figure 54 and Figure 55 As shown, valve actuator piston 900a is connected to the second camshaft 1012 via a fourth actuator lever 950, and valve actuator piston 900b is connected to the first camshaft 1000 via a first actuator lever 920. Figure 53 , Figure 54 , Figure 56 and Figure 57 As shown, valve actuator piston 900c is connected to the second camshaft 1012 via a fifth actuator lever 960, valve actuator piston 900d is connected to the third camshaft 1024 via a second actuator lever 930, valve actuator piston 900e is connected to the third camshaft 1024 via a sixth actuator lever 970, and valve actuator piston 900c is connected to the first camshaft 1000 via a third actuator lever 940.
[0635] like Figure 53 , Figure 54 and Figure 55As shown, the first actuator lever 920 includes a pivot anchor 922 comprising a partially cylindrical portion rotatably held within a conformal pivot socket 752 on a first side 750 of the frame 742, allowing the first actuator lever 920 to pivot about a first pivot axis 753 corresponding to the longitudinal axis of the partially cylindrical pivot anchor 922 and parallel to the first camshaft axis 1001, the second camshaft axis 1013, and the third camshaft axis 1025, respectively. The first actuator lever 920 includes a valve actuator piston engagement end 924 (e.g., a yoke with a semi-circular notch) opposite the pivot anchor 922, which receives a lever collar 908 and is seated on a lever seat 912 of a first valve actuator piston 900b arranged in a piston opening 746b formed in the bottom wall 744. In another example, the valve actuator piston does not have a reduced-width lever collar, and the lever seat is defined by the top of the spring housing 910, which has a width (e.g., diameter) greater than the width of the extension 906. The cam follower surface 926 of the first actuator lever 920 is engaged by a first cam lobe 1008 of the first camshaft 1000. As the first camshaft 1000 rotates about the first camshaft rotation axis 1001, the first cam lobe 1008 engages the cam follower surface 926 of the first actuator lever 920 once per revolution of the first camshaft 1000, causing the first actuator lever 920 to rotate about the first pivot axis 753 (counterclockwise in the example shown). When the first actuator lever 920 rotates due to engagement by the first cam cam lob 1008 of the first camshaft 1000, the piston engagement end 924 of the first actuator lever 920, seated on the lever seat 912 of the valve actuator piston 900b, pushes the valve actuator piston 900b downward to move it from its spring-biased first (valve closed) position to its second (valve open) position, thereby releasing (opening) the contact rod 902 of the valve actuator piston 900b and its associated valve (valve V14 in the illustrated example). As the first camshaft 1000 continues to rotate and the first cam lob 1008 disengages from the cam follower surface 926 of the first actuator lever 920, the spring 916, arranged in the spring chamber 914 of the spring housing 910, pushes the valve actuator piston 900b upward to close the associated valve again.
[0636] like Figure 53 , Figure 54 and Figure 56As shown, the second actuator lever 930 includes a pivot anchor 932 comprising a partially cylindrical portion rotatably held within a conformal pivot socket 752 on a first side 750 of the frame 742, allowing the second actuator lever 930 to pivot about a first pivot axis 753 corresponding to the longitudinal axis of the partially cylindrical pivot anchor 932. The second actuator lever 930 has an "L" shape, having a first leg extending from the pivot anchor 932 and a second leg extending laterally from the first leg, and includes a piston engagement 934 on one side of the second leg, having, for example, a semi-circular notch. This piston engagement receives a rod collar 908 and is seated on a lever seat 912 of a valve actuator piston 900d arranged in a piston opening 746d formed in the bottom wall 744. The cam follower surface 938 on the first leg of the second actuator lever 930 is engaged by the first cam lob 1030 of the third camshaft 1024. A first clearance curve 935 formed in the first leg of the second actuator lever 930 receives the first lobed portion 1002 of the second camshaft 1012, and a second clearance curve 936 formed in the second leg of the second actuator lever 930 receives the lobed portion 1026 of the third camshaft 1024. The first clearance curve 935 allows the first lobed portion 1002 of the first camshaft 1000 to rotate without affecting the second actuator lever 930 (imposing motion on it), and the second clearance curve 936 allows the lobed portion 1026 of the third camshaft 1024 to rotate without affecting the second actuator lever 930 (imposing motion on it). As the third camshaft 1024 rotates about its rotation axis 1025, the first cam cam lob 1030 engages once with the cam follower surface 938 of the second actuator lever 930 for each revolution of the third camshaft 1024, causing the second actuator lever 930 to rotate about its first pivot axis 753 (counterclockwise in the example shown). As the second actuator lever 930 rotates due to engagement by the first cam lob 1030 of the third camshaft 1024, the piston engagement 934, seated on the lever seat 912 of the valve actuator piston 900d, pushes the valve actuator piston 900d downward to move it from its spring-biased first (valve closed) position to its second (valve open) position, thereby releasing (opening) the contact rod 902 of the valve actuator piston 900d and its associated valve (valve V16 in the example shown). As the third camshaft 1024 continues to rotate and the first cam cam 1030 disengages from the cam follower surface 938 of the second actuator lever 930, the spring 916, arranged in the spring chamber 914 of the spring housing 910, pushes the valve actuator piston 900d upward, causing the contact rod 902 to close the associated valve again.
[0637] like Figure 53 , Figure 54 , Figure 56 and Figure 57 As shown, the third actuator lever 940 includes a pivot anchor 942 comprising a partially cylindrical portion rotatably held within a conformal pivot socket 752 on a first side 750 of the frame 742, allowing the third actuator lever 940 to pivot about a first pivot axis 753 corresponding to the longitudinal axis of the partially cylindrical pivot anchor 942. The third actuator lever 940 includes a piston engagement end 944 (e.g., a yoke with a semi-circular notch) opposite the pivot anchor 942, which receives a lever collar 908 and is seated on a lever seat 912 of a valve actuator piston 900f arranged in a piston opening 746f formed in the bottom wall 744. The cam follower surface 946 of the third actuator lever 940 is engaged by a second cam cam lobe 1010 of the first camshaft 1000. As the first camshaft 1000 rotates about its rotation axis 1001, the second cam cam lob 1010 engages the cam follower surface 946 of the third actuator lever 940 once per revolution of the first camshaft 1000, causing the third actuator lever 940 to rotate about its first pivot axis 753 (counterclockwise in the example shown). As the third actuator lever 940 rotates due to engagement by the second cam lob 1010 of the first camshaft 1000, the piston engagement end 944, seated on the lever seat 912 of the valve actuator piston 900f, pushes the valve actuator piston 900f downward, moving it from its spring-biased first (valve closed) position to its second (valve open) position, thereby releasing (opening) the contact rod 902 of the valve actuator piston 900f and its associated valve (valve V18 in the example shown). As the first camshaft 1000 continues to rotate and the second cam cam 1010 disengages from the cam follower surface 946 of the third actuator lever 940, the spring 916, arranged in the spring chamber 914 of the spring housing 910, pushes the valve actuator piston 900f upward, causing the contact rod 902 to close the associated valve again.
[0638] like Figure 53 , Figure 54 and Figure 55As shown, the fourth actuator lever 950 includes a pivot anchor 952 comprising a partially cylindrical portion rotatably held within a conformal pivot socket 756 on a second side 754 of the frame 742, allowing the fourth actuator lever 950 to pivot about a second pivot axis 757 corresponding to the longitudinal axis of the partially cylindrical pivot anchor 952 and parallel to the first camshaft axis 1001, the second camshaft axis 1013, and the third camshaft axis 1025, and parallel to the first pivot axis 753, respectively. The fourth actuator lever 950 includes a piston engagement end 954 (e.g., a yoke with a sem...
Claims
1. A component comprising: A first thermal module includes one or more thermal components, wherein each thermal component of the first thermal module includes: Thermal elements; and A thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface and at least one through hole extending through the thermal block, and wherein the thermal element and the associated thermal block of each thermal assembly are in thermal contact; A second thermal module includes one or more thermal components, wherein each thermal component of the second thermal module includes: Thermal elements; and A thermal block associated with the thermal element, wherein the thermal block has an exposed contact surface, wherein the thermal element and the associated thermal block of each thermal assembly are in thermal contact, and wherein each contact surface of the second thermal module is aligned and positioned opposite to the associated contact surface of the first thermal module. A thermal module actuator configured to enable automated relative movement between a first thermal module and a second thermal module to change the distance between the contact surface of each thermal component of the second thermal module and the associated contact surface of each thermal component of the first thermal module; and An optical fiber is associated with each through-hole of the thermal block extending through each thermal component of the first thermal module to transmit optical signals through each thermal block of the first thermal module.
2. A method comprising: A places the test platform, including the reaction chamber, between the first heater and the second heater; B enables automated movement of the first heater toward the second heater to clamp the reaction chamber between the first heater and the second heater; C utilizes the first heater and the second heater to apply heat energy to or absorb heat energy from the reaction mixture contained in the reaction chamber sandwiched between the first heater and the second heater; and During D, at least one optical signal is transmitted through a portion of the first heater via an optical fiber embedded within the first heater or extending completely or partially through the first heater.
3. A system for performing a measurement, the system comprising: A test platform, the test platform comprising at least one reaction chamber for containing a reaction mixture; as well as An instrument for applying thermal energy to the reaction chamber of the test platform and for transmitting optical signals to and / or from the reaction chamber, the instrument comprising: A first heater and a second heater are arranged in a relatively spaced-out configuration to receive the reaction chamber between the first heater and the second heater; An actuator is configured to, when the reaction chamber is arranged between the first heater and the second heater, move the first heater relative to the second heater to clamp the reaction chamber between the first heater and the second heater, by moving the first heater toward the second heater and / or by moving the second heater toward the first heater, wherein the first heater and the second heater apply heat energy to or absorb heat energy from the reaction chamber clamped between the first heater and the second heater; and An optical fiber, which at least partially extends through an aperture extending through the first heater and is configured to transmit optical signals through and / or from the reaction chamber via the first heater.
4. An instrument for receiving a fluid cartridge, wherein the fluid cartridge includes a sample chamber and a cap for closing the sample chamber, the instrument comprising: First rack; A second frame includes a box support bracket configured to hold a box located between the first frame and the second frame; An actuator is coupled to one or both of the first rack and the second rack and is configured to enable automated relative movement between the first rack and the second rack to change the distance between the first rack and the second rack; as well as A cassette detector is installed within the upper frame, wherein the cassette detector includes a plunger rod and a sensor, the plunger rod being configured to move between a first position and a second position, the sensor being configured to detect when the plunger rod is in the second position, and wherein, when the first frame and the second frame move toward each other relative to each other via the actuator, if the cassette is located on the cassette support bracket, the plunger rod will contact the cassette and move from the first position to the second position.
5. An instrument for applying thermal energy to a reaction chamber of a test platform, the instrument comprising: A first heater and a second heater are arranged in a spaced-apart configuration to receive the reaction chamber in a position relative to the first heater and the second heater, such that the first heater and the second heater contact different portions of the reaction chamber, and wherein each heater is configured to apply thermal energy to the reaction chamber by conductive heat transfer through a portion of the reaction chamber that is contacted by the respective heater. A first controller, configured to control the heat energy generated by the first heater; as well as A second controller is configured to control the heat generated by the second heater, wherein the heat generated by the first heater is controlled by the first controller independently of the heat generated by the second controller, and the heat generated by the second heater is controlled by the second controller independently of the heat generated by the first controller, and wherein the first controller controls the heat generated by the first heater and the second controller controls the heat generated by the second heater to achieve a common temperature distribution for the first heater and the second heater.
6. A method for applying thermal energy to a reaction chamber of a test platform, the method comprising: Heat energy is applied to the first and second sides of the reaction chamber using a first heater and a second heater, respectively. The heat energy generated by the first heater is controlled independently of the heat energy generated by the second heater; The heat energy generated by the second heater is controlled independently of the heat energy generated by the first heater; as well as The heat energy generated by the first heater and the heat energy generated by the second heater are controlled to achieve a common temperature distribution for the first heater and the second heater.
7. A method for controlling an injection pump, the injection pump comprising an elastomeric stop disposed within an injection barrel and a plunger connected to the stop, the method comprising: A operates a motor connected to the plunger in a first direction to move the plunger and the stop within the syringe barrel toward the bottom wall of the syringe barrel; B monitors a motor demand signal for the motor while operating the motor in the first direction, wherein the motor demand includes motor operating parameters that are directly or indirectly proportional to the motor output. C detects a bend in the motor demand signal, wherein the bend in the motor demand signal indicates that the stop has contacted the bottom wall of the injection cylinder; After detecting the bend, D continues to operate the motor in the first direction until the motor stalls; E counts the encoder step size of the encoder connected to the motor after detecting the bend and until the motor stalls. F operates the motor in the second direction to reach the number of encoder step distances counted in E; as well as Following F, G continues to operate the motor in the second direction to move the stop a predetermined distance away from the bottom wall of the syringe to draw a predetermined volume of fluid into the syringe body.
8. A cartridge for detecting an analyte of interest from a reaction mixture by exposing the reaction mixture to an excitation optical signal and detecting the presence or absence of an emission optical signal from the reaction mixture, the cartridge comprising: A box body having a first surface, a second surface, at least one opening extending from the first surface to the second surface, and one or more grooves formed in the second surface; A first film is attached to a first surface of the housing body and covers a first end of the at least one opening, wherein the first film comprises a transparent or translucent material to allow optical signals to pass through the first film into or out of the at least one opening; A second film is attached to a second surface of the box body and covers the one or more grooves to form one or more channels that traverse a portion of the second surface, wherein the second film covers a portion of the second surface that is spatially separated from the at least one opening; as well as A thermally conductive laminated seal is attached to a second side of the housing body and covers a second end of the at least one opening, wherein the at least one opening covered by the first film and the thermally conductive laminated seal defines a reaction chamber for receiving the reaction mixture, wherein the thermally conductive laminated seal comprises: A plastic layer is attached to the second side of the box body and covers the second end of the at least one opening; as well as A conductive layer is attached to the surface of the plastic layer opposite to the surface of the plastic attached to the second side of the box body.
9. A cartridge that can detect the presence or absence of an analyte of interest contained in the reaction mixture within the cartridge by exposing the reaction mixture to an excitation optical signal and detecting the presence or absence of an emission optical signal from the reaction mixture, the cartridge comprising: A cartridge body having one or more reaction chambers, each reaction chamber being configured to receive a reaction mixture, wherein one wall of each reaction chamber is transparent or translucent to allow optical signals to enter or exit the reaction chamber through the wall, and wherein each reaction chamber is open to the surface of the cartridge body; A film is attached to the surface of the box body and covers a first portion of the surface of the box body, wherein the first portion of the surface is spatially separated from the reaction chamber open to the surface; as well as A thermally conductive laminated seal is attached to a second portion of the surface of the housing body, wherein the second portion of the surface closes the reaction chamber open to the surface, and the thermally conductive laminated seal closes the reaction chamber, and wherein the thermally conductive laminated seal comprises: A plastic layer is attached to a second portion of the surface of the box body and closes the reaction chamber; as well as A conductive layer is attached to the surface of the plastic layer opposite to the surface of the second portion of the plastic attached to the surface of the box body.
10. A system for applying heat energy to a reaction mixture and for transmitting optical signals to and / or from the reaction mixture, the system comprising: A reaction chamber for receiving the reaction mixture, wherein a first wall of the reaction chamber is transparent or translucent, and a second wall of the reaction chamber includes a thermally conductive laminated seal, wherein the thermally conductive laminated seal includes a plastic layer facing the interior space of the reaction chamber and a conductive layer disposed on the plastic layer; A first heater, which is in contact with or configured to be placed in contact with a first wall of the reaction chamber, heats the reaction mixture within the reaction chamber by means of conductive heat transfer to the first wall in contact with the first heater. A second heater, which is in contact with a second wall of the reaction chamber, heats the reaction mixture within the reaction chamber by means of conductive heat transfer to the reaction chamber through the second wall in contact with the second heater. as well as An optical waveguide, which extends at least partially through the first heater and is configured to transmit optical signals through the first heater and the first wall to the reaction mixture contained in the reaction chamber and / or through the first wall and the first heater to transmit optical signals from the reaction mixture contained in the reaction chamber.
11. A method for applying heat energy to a reaction mixture and for transmitting optical signals to and / or from the reaction mixture, wherein the reaction mixture is contained within a reaction chamber having a transparent or translucent first wall and a second wall including a thermally conductive laminated seal, wherein the thermally conductive laminated seal includes a plastic layer facing the interior space of the reaction chamber and a conductive layer disposed on the plastic layer, the method comprising: The reaction mixture inside the reaction chamber is heated by bringing the first wall of the reaction chamber into contact with the first heater and by transferring conductive heat energy to the first wall of the reaction chamber that is in contact with the first heater. The reaction mixture within the reaction chamber is heated by bringing the second wall of the reaction chamber into contact with the second heater and by conductive heat transfer to the reaction chamber through the second wall in contact with the second heater; and Optical signals are transmitted through the first heater and the first wall to the reaction mixture contained in the reaction chamber via an optical waveguide that extends at least partially through the first heater, and / or optical signals from the reaction mixture contained in the reaction chamber are transmitted through the first wall and the first heater via the optical waveguide.
12. A method of manufacturing a fluid cartridge, the method comprising: A first film is attached to a box body, wherein the box body has a first side, a second side, and at least one opening in the box body extending from the first side to the second side, wherein the first film is fixed to at least a portion of the first side to cover a first end of the at least one opening; as well as A thermally conductive laminated seal is attached to a portion of a second side of the housing body to cover the second end of the at least one opening, wherein the thermally conductive laminated seal comprises a plastic layer facing the at least one opening and a conductive layer disposed on the plastic layer.
13. A method of manufacturing a fluid cartridge, the method comprising: A first film is attached to a box body, wherein the box body has a first side, a second side, and at least one opening in the box body extending from the first side to the second side, wherein the first film is fixed to at least a portion of the first side to cover a first end of the at least one opening; A seal is attached to at least a portion of the second side of the box body to cover the second end of the at least one opening, wherein the seal includes a plastic layer facing the at least one opening; as well as Before or after attaching the seal to a portion of the second side of the box body, a desiccant is adhered to at least a portion of the surface of the plastic layer of the seal facing the at least one opening.
14. A method of manufacturing a fluid cartridge, the method comprising: A first film is attached to a box body, wherein the box body comprises plastic and has a first side, a second side and at least one opening in the box body extending from the first side to the second side, wherein the first film is secured to at least a portion of the first side to cover a first end of the at least one opening; as well as The seal is attached to at least a portion of the second side of the housing body to cover the second end of the at least one opening, wherein the housing body includes one or more energy conductors formed on the second side and at least partially surrounding each of the at least one opening, wherein the seal includes a plastic layer facing the at least one opening, and wherein attaching the seal to the second side of the housing body includes heat-sealing or ultrasonically welding the plastic layer of the seal to the housing body by melting the energy conductor and melting the melted energy conductor with the plastic layer.
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