Pneumatic siphon valve and reaction chamber for sample analysis

Abstract

A rotatable device includes an exhaust port, a siphon, and a ballast chamber. The siphon has a top portion positioned radially outside the exhaust port relative to the axis of rotation. The ballast chamber has a first outlet connected to the exhaust port and a second outlet connected to an inlet of the siphon. The first outlet of the ballast chamber is positioned radially inside the second outlet of the ballast chamber and radially outside the top of the siphon relative to the axis of rotation. Thus, the first outlet of the ballast chamber divides the ballast chamber into an unventilated ballast portion radially within the first outlet and a ventilated ballast portion radially outside the first outlet, and thus isolates pressure variations within the ballast chamber from a radial location of the siphon inlet at the ballast chamber.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 489,420, filed March 9, 2023, and U.S. Provisional Patent Application No. 63 / 489,667, filed March 10, 2023. The disclosure of each application is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] This disclosure relates to apparatus and methods for guiding fluids, mixing fluids, and / or resuspending reagents in centrifugal microfluidics. Background Technology

[0004] Currently, 70% of medical decisions rely on laboratory diagnostics, but the diagnostic process is now disconnected from how care is delivered. Primary healthcare systems require patients to travel to external blood collection points, where the blood is then shipped to laboratories and processed overnight. This means that laboratory results don't reach healthcare professionals until long after the patient has left. This friction in healthcare services and disease management leads to enormous waste within the healthcare system.

[0005] a. Patients frequently postpone laboratory tests or fail to comply with laboratory test or follow-up care recommendations.

[0006] b. Gaps in the diagnostic process can lead to missed examinations, misdiagnosis, and lack of intervention, ultimately resulting in adverse outcomes.

[0007] c. Healthcare professionals waste time tracking lab orders and patient visit records. This wastes even more time reaching out to patients and advancing subsequent steps in the patient care pathway when intervention is needed.

[0008] These problems are even more pronounced when caring for rural populations or patient groups facing adverse social health determinants, as there are many challenges in ensuring successful follow-up from the initial patient visit.

[0009] Several companies have manufactured point-of-care diagnostic instruments to bridge this gap. However, these instruments are limited to single-type tests and cannot fully meet the workflow needs of primary healthcare providers for a single system that produces simple, comprehensive, and rapid test results. A product is currently under development to meet these needs. This product achieves this through a highly automated workflow implemented using centrifugal microfluidic disks.

[0010] Centrifugal microfluidics is used in clinical chemistry, immunoassays, hematology, medicine, biomedical research, and other fields. Many of these applications use a non-ventilated chamber connected to a siphon channel as a pressure-dependent valve. However, pressure variations in such valves depend on the radial position of the siphon inlet within the chamber. Additionally, many of these applications require stopping the chamber during certain workflows to meet various cleaning requirements. However, existing valve designs, such as conventional pneumatic siphons, simple siphon metering valves, and capillary siphon valves, are insufficient for these applications.

[0011] Therefore, there is still a need for improved devices and methods in centrifugal microfluidics. Summary of the Invention

[0012] This disclosure addresses these and other needs in the art by providing the following: (i) a siphon valve structure that isolates pressure variations in the chamber from the radial location of the siphon inlet in the chamber and / or occupies less space on the casing; (ii) a reusable siphon valve structure independent of residual fluid; and (iii) a centrifugation apparatus and method that not only retains magnetic particles while cleaning the reaction chamber to remove all unwanted components, but also allows these particles to be moved back into the main reaction chamber and homogenize the mixture.

[0013] In one aspect, this disclosure provides a device rotatable about a rotation axis. The device includes an exhaust port, a siphon, a ballast chamber, and / or other components disclosed herein (e.g., a U-shaped channel described below) to allow liquid to enter the ballast chamber without allowing air to escape from it. The siphon has a top positioned radially outside the exhaust port relative to the rotation axis. The ballast chamber has a first outlet connected to the exhaust port and a second outlet connected to the inlet of the siphon. The first outlet of the ballast chamber is positioned radially within the second outlet of the ballast chamber and radially outside the top of the siphon relative to the rotation axis, thereby dividing the ballast chamber into a non-ventilated ballast portion radially within the first outlet and a ventilated ballast portion radially outside the first outlet. In some embodiments, the second outlet of the ballast chamber is formed at or near the radially outermost position of the ballast chamber.

[0014] In some embodiments, the device further includes: a first channel connecting the first outlet of the ballast chamber to the exhaust port; an upstream chamber connected to the ballast chamber; a U-shaped channel connecting the ballast chamber to the upstream chamber; a downstream chamber connected to the outlet of the siphon; or any combination thereof.

[0015] In some embodiments, the ballast chamber includes an inlet located in the non-ventilated ballast section, and the upstream chamber is connected to the inlet located in the non-ventilated ballast section of the ballast chamber. In some embodiments, the upstream chamber includes an outlet connected to the ballast chamber, and the top of the siphon and the vent are radially located within the outlet of the upstream chamber. In some such embodiments, the outlet of the upstream chamber is formed at the outermost radial position of the upstream chamber.

[0016] In some embodiments, the volume between the radial positions of the first outlet and the second outlet in the ballast chamber is greater than the volume required to extend beyond the top of the siphon. In some embodiments, the downstream chamber is positioned radially outside the ballast chamber.

[0017] In some embodiments, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow initial loading of the fluid by rotating the device at a speed that causes the fluid to fill the ballast chamber and the siphon, thereby forming a first meniscus radially within the first outlet in the ballast chamber and a second meniscus radially outside the top of the siphon in the siphon.

[0018] In some embodiments, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow the upstream chamber to be emptied by reducing the speed. Alternatively, in some embodiments, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow the upstream chamber to be emptied by increasing the speed.

[0019] In some implementations, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof are configured to allow complete emptying of the upstream chamber.

[0020] In another aspect, this disclosure provides a device capable of rotating about a rotation axis. The device includes a chamber, an appendage, and magnetic particles. The appendage includes an inlet connected to the chamber and a trapping area radially outside the inlet relative to the rotation axis. The magnetic particles are movable between the chamber and the appendage by means of a magnet, positioning the chamber relative to the magnet, rotating the device, or any combination thereof.

[0021] In some embodiments, the chamber includes a flexible overlay that responds to one or more acoustic pulses to facilitate mixing of the magnetic particles with the fluid within the chamber. In some embodiments, the magnetic particles are magnetic nanoparticles.

[0022] In another aspect, this disclosure provides a method comprising (A) placing a chamber of an apparatus near a magnet such that magnetic particles contained in the chamber form a first alignment. The apparatus includes an appendage having an inlet connected to the chamber and a trapping region radially outside the inlet relative to a rotation axis of the apparatus. The method further comprises (B) rotating the apparatus relative to the magnet in a first direction to move the magnetic particles into the appendage connected to the chamber. The method further comprises (C) rotating the apparatus at a certain speed to flush out unbound analytes or non-specifically bound particles from the chamber. The rotation (C) causes the magnetic particles to move into and remain in the trapping region.

[0023] In some embodiments, the placement (A) is performed by rotating the device. In some embodiments, the magnet generates the strongest magnetic field in the central portion of the chamber. In some embodiments, the rotation (B) is performed continuously. Alternatively, in some embodiments, the rotation (B) is performed intermittently.

[0024] In some embodiments, the method further includes (D) filling the chamber with fluid after the rotation (C), and (E) rotating the device relative to the magnet in a second direction to move the magnetic particles from the appendage into the chamber. In some embodiments, the rotation (E) is performed continuously. Alternatively, in some embodiments, the rotation (E) is performed intermittently.

[0025] In some embodiments, where the chamber includes a flexible covering layer, the method further includes: (F) aligning the chamber with an ultrasonic probe; (G) moving the ultrasonic probe or the device such that the ultrasonic probe contacts the flexible covering layer; and (H) activating the ultrasonic probe to emit one or more pulses to promote mixing of the magnetic particles with the fluid.

[0026] In some embodiments, the alignment (F) is achieved by rotating the device. In some embodiments, the alignment (F), the movement (G), and the activation (H) are performed before the placement (A). In some embodiments, the alignment (F), the movement (G), and the activation (H) are performed after the rotation (E).

[0027] In some embodiments, the method further includes (I) allowing the mixture in the chamber to incubate for a period of time after the activation (H).

[0028] The apparatuses, systems, and methods disclosed herein have other features and advantages that will be apparent from or set forth in more detail in the accompanying drawings incorporated herein and in the following detailed description, which together serve to explain certain principles of the exemplary embodiments of this disclosure. Attached Figure Description

[0029] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate one or more exemplary embodiments of the present disclosure and, together with the specific embodiments, serve to explain the principles and implementation of the exemplary embodiments of the invention. The drawings are not necessarily drawn to scale. Specific design features of the invention disclosed herein (including, for example, specific dimensions, orientations, positions, and shapes) will be determined in part by the specific intended application and environment of use. Furthermore, the components shown in the figures can be combined in any useful number and combination.

[0030] In the attached diagram:

[0031] Figure 1A This is a schematic diagram illustrating an apparatus according to some exemplary embodiments of the present disclosure;

[0032] Figure 1B and Figure 1C The figures illustrate some exemplary embodiments according to this disclosure. Figure 1A A schematic diagram of the siphon valve structure of the device;

[0033] Figure 2A The figures illustrate the use of some exemplary embodiments according to this disclosure. Figure 1A A schematic diagram of the operation process of the device;

[0034] Figure 2B This is a schematic diagram illustrating an apparatus according to an alternative exemplary embodiment of the present disclosure;

[0035] Figure 2C This is a schematic diagram illustrating an apparatus according to another alternative exemplary embodiment of the present disclosure;

[0036] Figure 3A These are images illustrating apparatuses according to some exemplary embodiments of the present disclosure;

[0037] Figure 3B yes Figure 3A A magnified view of a portion of the image;

[0038] Figure 3C The figures illustrate some exemplary embodiments according to this disclosure. Figure 3AA schematic diagram of one (or more) components of the device;

[0039] Figure 4 This is a flowchart illustrating a method according to some exemplary embodiments of the present disclosure;

[0040] Figure 5A , Figure 5B , Figure 5C and Figure 5D The figures together illustrate the use of some exemplary embodiments according to this disclosure. Figure 4 Images of the process performed by device A;

[0041] Figure 6A This is a schematic diagram illustrating an apparatus (e.g., a disk) according to some exemplary embodiments of the present disclosure;

[0042] Figure 6B This is a schematic diagram illustrating a loading process according to some exemplary embodiments of the present disclosure;

[0043] Figure 6C This is a schematic diagram illustrating a spin process according to some exemplary embodiments of the present disclosure;

[0044] Figure 6D This is a schematic diagram illustrating the startup process according to some exemplary embodiments of the present disclosure;

[0045] Figure 6E-1 This is a schematic diagram illustrating the injection and mixing process according to some exemplary embodiments of the present disclosure;

[0046] Figure 6E-2 yes Figure 6E-1 A magnified view of a portion of the image;

[0047] Figure 6F-1 This is a schematic diagram illustrating the freeze-dried bead reconstruction and pull-down process according to some exemplary embodiments of the present disclosure;

[0048] Figure 6F-2 yes Figure 6F-1 A magnified view of a portion of the image;

[0049] Figure 6G-1 This is a schematic diagram illustrating a cleaning process according to some exemplary embodiments of the present disclosure;

[0050] Figure 6G-2 yes Figure 6G-1 A magnified view of a portion of the image;

[0051] Figure 6H-1 This is a schematic diagram illustrating the reconstruction and incubation process of freeze-dried beads of the report according to some exemplary embodiments of the present disclosure;

[0052] Figure 6H-2 yes Figure 6H-1 A magnified view of a portion of the image;

[0053] Figure 6I-1 This is a schematic diagram illustrating a particle pull-down and cleaning process according to some exemplary embodiments of the present disclosure;

[0054] Figure 6I-2 yes Figure 6I-1 A magnified view of a portion of the image;

[0055] Figure 6J This is a schematic diagram illustrating the resuspended particles and readout process according to some exemplary embodiments of the present disclosure; and

[0056] Figure 7 This is a schematic diagram illustrating an apparatus (e.g., a disk) according to an alternative exemplary embodiment of the present disclosure. Detailed Implementation

[0057] Volume-independent pneumatic siphon valve

[0058] In microfluidics, many applications use a non-ventilated chamber connected to a siphon channel as a pressure-dependent valve. However, pressure variations in such a valve depend on the radial position of the siphon inlet within the chamber. Additionally, such valves may require a relatively large amount of space in the housing to function properly. This disclosure addresses these and / or other requirements by providing a siphon valve structure that isolates pressure variations within the chamber from the radial position of the siphon inlet within the chamber and / or occupies less space in the housing.

[0059] Referring now to the accompanying drawings, in which the same reference numerals always indicate the same elements. Figure 1A An exemplary device 100 with an exemplary siphon valve structure 110 is shown according to some embodiments of the present disclosure. Device 100 may be a microfluidic disk, cassette, etc., for sample handling or processing. In various embodiments, device 100 is rotatable about a rotation axis 102.

[0060] The siphon valve structure 110 typically includes an exhaust port 120, a siphon tube 130, and a ballast chamber 140. The siphon tube has a top 132 positioned radially outside the exhaust port relative to the axis of rotation of the device. The ballast chamber has a first outlet 142 connected to the exhaust port and a second outlet 143 connected to the siphon tube (e.g., the inlet of the siphon tube). The first outlet 142 of the ballast chamber is positioned radially inside the second outlet 143, but radially outside the top 132 of the siphon tube. Thus, the first outlet 142 divides the ballast chamber into a first portion 146 and a second portion 148. The first portion 146 is the portion radially outside the first outlet 142, while the second portion 148 is the portion radially inside this outlet.

[0061] Due to the presence of the vent, when the fluid is in the first part of the ballast chamber, such as Figure 1B As shown, the position of the fluid meniscus does not affect the pressure in the ballast chamber. Therefore, the first section 146 is referred to herein as the ventilation section. However, when the fluid is in the second section, the position of the fluid meniscus affects the pressure in the ballast chamber because the fluid blocks the air passage to the exhaust port, as... Figure 1C As shown. Therefore, the second section 148 is referred to herein as the non-ventilated section. Because the first outlet 142 is radially within the second outlet 143, pressure changes in the ballast chamber are independent of the location of the second outlet 143, which defines the radial location of the siphon inlet. This isolates pressure changes in the ballast chamber from the radial location of the siphon inlet.

[0062] The first and second outlets of the ballast chamber can be formed at any suitable location, provided that the radial position of the first outlet 142 of the ballast chamber is between the second outlet 143 and the top 132 of the siphon. As a non-limiting example, Figure 1 illustrates that the second outlet 143 of the ballast chamber is formed at or near the outermost position in the radial direction of the ballast chamber.

[0063] Device 100 or siphon valve structure 110 may include additional, optional, or alternative components. For example, in some embodiments, device 100 or siphon valve structure 110 includes a passage 150 connecting a first outlet of the ballast chamber to an exhaust port, an upstream chamber 160 connected to the ballast chamber, a U-shaped passage 170 connecting the ballast chamber to the upstream chamber, a downstream chamber 180 connected to the siphon outlet, or any combination thereof. In some embodiments, the U-shaped passage 170 may have an outward section and an inward section, such as... Figures 1A to 1C And / or as shown in other figures disclosed herein.

[0064] In some embodiments, the ballast chamber includes an inlet 141 located in a non-ventilated ballast section, and the upstream chamber includes an outlet 161 connected to the inlet 141 of the ballast chamber, for example, via a U-shaped channel 170. In some embodiments, the outlet of the upstream chamber is formed at the radially outermost position of the upstream chamber. In some embodiments, the top of the siphon and the vent are radially located within the outlet of the upstream chamber. In some embodiments, the downstream chamber is positioned radially outside the ballast chamber. In some embodiments, the ballast chamber and the U-shaped channel are configured such that the volume in the ballast chamber from the inward position of the first outlet 142 is greater than the volume required beyond the top of the siphon, and in some embodiments, it may be greater than the volume of the U-shaped channel.

[0065] In some embodiments, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow initial loading of the fluid by rotating the device at a speed that causes fluid to fill the ballast chamber and the siphon, thereby forming a first meniscus radially within the first outlet 142 inside the ballast chamber and a second meniscus radially outside the siphon top 132 inside the siphon. In some exemplary embodiments, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow emptying of the upstream chamber by changing (e.g., decreasing or increasing) the rotation speed. In some embodiments, the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow complete emptying of the upstream chamber by changing the rotation speed.

[0066] For example, during rotation at the initial rotational speed, the ballast chamber is filled with liquid until the pneumatic pressure in the ballast chamber matches the available centrifugal force, such as... Figure 2A As shown. The liquid position 144 inside the ballast chamber depends on several factors, such as the rotational speed, the liquid meniscus position 145 on the upstream chamber, the radial position 146 of the U-shaped channel outlet, the air pressure inside the chamber, the geometry of the ballast chamber 140, and / or the radial position of the first ballast outlet 142. In some embodiments, at this initial rotational speed, these factors are adjusted such that the liquid meniscus position on the siphon is radially outside the top 132. This prevents liquid flow, and the structure acts as a valve in the closed position. By changing the rotational speed, the combined effect of the air pressure and centrifugal force in the ballast chamber pushes the liquid into the siphon outlet, past the top of the siphon, and then drains the liquid into the downstream chamber, thus causing the valve to "open". Because the air pressure only increases after the liquid fills the vent inlet (corresponding to the first outlet 142 of the ballast chamber) rather than the siphon inlet (corresponding to the second outlet 143 of the ballast chamber), this allows for the isolation of the total volume to be emptied from the volume used to generate air pressure in the ballast chamber.

[0067] In some embodiments, the exhaust port, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow the upstream chamber to be emptied by reducing the velocity. For example, as a non-limiting example, Figure 2AThe diagram illustrates an embodiment that allows emptying when the speed decreases after the initial rotational step (e.g., the starting speed is lower than the initial speed). In a specific implementation, the initial rotational speed can be approximately 2900 rpm, and the starting speed can be approximately 2500 rpm. The upstream chamber liquid meniscus radius 145 can be approximately 13.2 mm, the main chamber inlet radius 146 can be approximately 19 mm, the volume of the non-ventilated portion of the main chamber 140 can be approximately 6 μL, the radius of the siphon top 132 can be approximately 13 mm, the width of the ballast chamber 140 can be approximately 1.2 mm, the depth can be approximately 0.6 mm, and the radius t of the first outlet 142 of the main chamber can be approximately 20.5 mm.

[0068] In some embodiments, the exhaust port, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, are configured to allow the upstream chamber to be emptied by increasing the velocity. For example, as a non-limiting example, Figure 2B The diagram illustrates an implementation that allows emptying when the speed is increased after the initial rotational step (e.g., the starting speed is higher than the initial speed). In a specific implementation, the initial rotational speed can be approximately 3000 rpm, and the starting speed can be approximately 4300 rpm. During the initial rotational speed, the upstream chamber liquid meniscus radius 145 can be approximately 16 mm, the main chamber inlet radius 146 can be approximately 19 mm, the volume of the non-ventilated portion of the main chamber 140 can be approximately 6 μL, the siphon top radius 132 can be approximately 16.5 mm, the ballast chamber 140 can be approximately 1.2 mm wide, approximately 0.6 mm deep, and the radius of the first outlet 142 of the main chamber can be approximately 20.5 mm. After accelerating to a higher starting speed, the liquid meniscus on the upstream chamber will move outward to position 148, and the liquid meniscus radius within the main ballast will move inward to position 147. This will cause the liquid meniscus position within the siphon channel to move inward past the siphon top 132, then drain the liquid into the downstream chamber and thus cause the valve to "open".

[0069] As yet another non-restrictive example, Figure 2C The diagram illustrates the shape or position of some components of the device. Figure 2A and Figure 2C The shape or position of the ballast varies with different implementations. In a specific implementation, the initial rotational speed can be approximately 3500 rpm, and the starting speed can be approximately 3100 rpm. The upstream chamber liquid meniscus radius 145 can be approximately 27.5 mm, the main chamber inlet radius 146 can be approximately 36 mm, the volume of the non-ventilated portion of the main chamber 140 can be approximately 1.8 μL, the siphon top radius 132 can be approximately 31 mm, the ballast chamber width can be approximately 1.3 mm, the depth can be approximately 0.8 mm, and the R-shaped ballast can be approximately 41 mm.

[0070] refer to Figures 2D to 2G The diagram shows the liquid position of a device with a siphon valve structure 110 during operation according to some embodiments of the present disclosure. Figure 2D The liquid in the initial filling step is shown. Figure 2E The liquid is shown in the steady state of its initial rotational velocity. Figure 2F The liquid in the startup step is shown. Figure 2D The liquid during the evacuation step is shown.

[0071] Although Figure 2A , Figure 2B and Figure 2C The illustrations show components with specific shapes, and the corresponding paragraphs provide some specific values ​​for configuration / operation parameters; however, it should be noted that these are merely examples, and the invention is not limited thereto. The device and / or siphon valve structure may be configured with additional, optional, or alternative components, which may have different shapes and / or sizes, may be arranged in different locations, may operate at different speeds, etc.

[0072] The siphon valve structure disclosed herein offers several advantages. The structure allows for greater design flexibility and a more compact design, particularly when the volume required for pneumatic control is smaller than the volume required for extraction from the ballast chamber. The structure also provides a size advantage, as a large pressure can be generated even with a small volume of compressed air chamber, despite the extraction of a significant amount of fluid. Furthermore, the structure allows multiple chambers to operate at the same speed / volume, regardless of the volume to be emptied. The structure can achieve higher pressures and allows for a wider range of operating speeds. Additionally, the structure allows for the integration of more functions into the device (e.g., a tray or box) for greater operational flexibility and / or adjustments to meet desired workflow requirements.

[0073] Volume-independent reusable pneumatic siphon valve

[0074] Many applications, such as immunoassay of centrifugally sensitive particles and reaction processes that benefit from multiple cleaning steps, often require stopping the siphon during certain workflow steps. However, existing valve designs, such as conventional pneumatic siphons, simple siphon metering valves, and capillary siphon valves, cannot meet the needs of these applications. For example, after initial purging and stopping, conventional pneumatic siphons are difficult to restart at the same operating speed because some residual volume often remains in the neutral chamber of the U-channel, which enters the main chamber during subsequent speed increases. Due to the presence of residual liquid, the volume of the gas chamber to be compressed will not be as defined as under initial conditions, making conventional pneumatic siphons unreliable after initial use. Simple siphon metering valves simply delay the liquid flow until it reaches a certain level and rely on upstream structures to control the liquid volume. Capillary siphon valves rely on capillaries to wet and initiate the siphon. Because capillaries depend on surface properties, capillary siphon valves are sensitive to the liquid being processed and the manufacturing methods used to make the valve. When capillary siphon valves are wetted by different liquids, they may also have different operating ranges.

[0075] This disclosure addresses these and / or other needs by providing a reuse siphon valve structure that is independent of residual fluid. The structure features a hybrid valve control configuration that allows for sequential liquid delivery while maintaining a more compact, single metering structure with higher levels of control and / or accuracy.

[0076] The overall concept of the reused siphon valve structure is similar to or the same as the siphon valve structure 110 disclosed herein. Because the ballast chamber 140 is connected to the exhaust port 120, the ballast chamber is divided into two parts, one ventilated and one non-ventilated. Therefore, as long as the remaining fluid meniscus remains within the ventilated section (e.g., not exceeding the radial position of the first outlet 142), the remaining liquid will not affect the pressure within the ballast chamber. Even when there is some remaining liquid, this allows for independent control of the pressure within the chamber and the reuse of the siphon valve structure with a high level of control and / or precision.

[0077] In some implementation schemes, such as Figure 2C In the outlined embodiment, the ballast chamber 140 and the U-shaped channel 170 are configured such that the second outlet 143 of the ballast chamber (corresponding to the inlet of the siphon) is located at the outermost radial position of the ballast chamber, and the volume within the ballast chamber extending inward from outlet 142 is greater than the volume required beyond the top of the siphon, and in some embodiments, may be greater than the volume of the U-shaped channel. This allows for multiple reuses of the same valve structure and thus makes the same volume of valve core space more efficient.

[0078] In some implementations, the operating speed is adjusted to ensure that the upstream chamber is completely emptied. For example, in some implementations, the operation may include rotating the device at an initial speed to fill one or more chambers (e.g., the upstream chamber), changing the speed to empty one or more chambers, slowing down or stopping the rotation if necessary, and repeating these steps as many times as desired.

[0079] Effective and efficient magnetic particle reaction chamber

[0080] Magnetic particles, after appropriate functionalization, can be used as components of reactions. Magnetic particles are useful when it is necessary to wash away unbound reagents and sample interferences from specifically bound analytes or reporter substances. If such reactions are performed using a centrifuge, it is necessary to retain these particles while washing away unwanted components. For centrifuges without any active magnetic elements, an external magnetic field is required to hold the magnetic particles while washing them to remove unwanted components. If the external magnetic field cannot follow the rotation of the centrifuge to achieve the washing purpose, a specific feature is needed in the device to hold the magnetic particles. This feature needs to be able to retain and release the magnetic particles when needed. Another challenge in using magnetic particles in reactions is the need to redisperse / homogenize the magnetic particles back into solution to achieve efficient reaction kinetics.

[0081] This disclosure addresses these and / or other needs by providing a centrifugation apparatus and method that not only retains magnetic particles while cleaning the reaction chamber to remove all unwanted components, but also allows these particles to move back to the main reaction chamber and homogenize the mixture.

[0082] refer to Figures 3A to 3C An exemplary device 300 according to some embodiments of the present disclosure is shown. The device is rotatable about a rotation axis 302. The device 300 includes a chamber 310, an appendage 320, and magnetic particles 330. The appendage 320 includes an inlet 322 connected to the chamber 310 and a trapping area 324 radially outside the inlet relative to the rotation axis. When the device is manufactured, the magnetic particles are placed in the chamber or the appendage. The chamber and appendage are configured such that the magnetic particles can move between the chamber and the appendage via a magnet, a chamber positioned relative to a magnet, a rotating device, or any combination thereof. In some embodiments, the magnetic particles are magnetic nanoparticles.

[0083] In some embodiments, chamber 310 includes a flexible covering layer 312; for example, one of the chamber walls is made of a flexible material. The flexible covering layer responds to one or more acoustic pulses to facilitate the mixing of magnetic particles with the fluid within the chamber. For example, this allows for rapid homogenization of the reaction mixture using an ultrasonic probe without the addition of any additional features and / or reaction volume.

[0084] refer to Figure 4 The diagram illustrates a flowchart of an exemplary method 400 for mixing fluids according to some embodiments of the present disclosure. In the flowchart, preferred portions of the method are shown in solid boxes, while additional, optional, or alternative portions of the method are shown in dashed boxes. It should be noted that the processes illustrated herein and in the flowchart may, but not all, be performed or performed in the order they are presented.

[0085] Referring to block 402, in some embodiments, the method includes (A) placing a chamber of the device near a magnet such that the magnetic particles contained in the chamber form a first alignment. For example, in some embodiments, the method includes placing chamber 310 of device 300 near a magnet, such as... Figure 5A As shown. In some embodiments, the placement (A) is performed by rotating the device. Alternatively, in some exemplary embodiments, the placement (A) is performed by moving the magnet or by moving both the magnet and the device. In some embodiments, the magnet generates the strongest magnetic field in the central portion of the chamber.

[0086] Referring to block 404, in some embodiments, the method further includes (B) rotating the device relative to the magnet in a first direction to move the magnetic particles into an appendage connected to the chamber, wherein the appendage includes an inlet and a capture area radially outside the inlet relative to the axis of rotation of the device. For example, as Figure 5B and Figure 5C As shown, when the device rotates relative to the magnet, magnetic particles move from chamber 310 to appendage 320 connected to the chamber. The rotation of the device can be continuous (e.g., smoothly rotating from one position to another without interruption) or intermittent (e.g., at a set of angular positions).

[0087] Referring to block 406, in some embodiments, the method further includes (C) rotating the device at a certain speed to flush unbound analytes or non-specifically bound particles out of the chamber. The magnetic particles remain in the trapping area. For example, as... Figure 5C and Figure 5D As shown, when the device rotates at a certain speed to flush out unbound analytes or non-specifically bound particles from the chamber, magnetic particles remain in the device during the flushing process. In some embodiments, when the device rotates at high speed, magnetic particles remain in the capture zone, and any liquid in the chamber can overflow to another reservoir without any loss of magnetic particles.

[0088] Referring to block 408, in some embodiments, the method includes (D) filling the chamber with fluid after the rotation (C).

[0089] Referring to block 410, in some embodiments, the method includes (E) rotating the device relative to the magnet to move the magnetic particles from the appendage to the chamber. The rotation of the device may be continuous or intermittent (e.g., in a set of angular positions).

[0090] Referring to block 412, in some embodiments, the method includes (F) aligning the chamber with an ultrasonic probe. In some embodiments, the alignment (F) is achieved by rotating the device.

[0091] Referring to block 414, in some embodiments, the method includes (G) moving the ultrasonic probe or the device such that the ultrasonic probe comes into contact with the flexible cover layer.

[0092] Referring to block 416, in some embodiments, the method includes (H) activating the ultrasonic probe to emit one or more pulses to facilitate mixing of the magnetic particles with the fluid.

[0093] Referring to block 418, in some embodiments, the method includes (I) allowing the mixture in the chamber to incubate for a period of time after the activation (H).

[0094] In some embodiments, the alignment (F), the movement (G), and the activation (H) are performed before the placement (A). In some embodiments, the alignment (F), the movement (G), and the activation (H) are performed after the rotation (E). In some embodiments, the relative movement between the magnet and the chamber is achieved by moving a magnet, a device, or both. In some embodiments, the method includes repeating any one of the steps disclosed above.

[0095] refer to Figure 7 This document illustrates an alternative exemplary embodiment of an apparatus 700 (e.g., a disc) according to the present disclosure. In some embodiments, the apparatus 700 (e.g., a disc) includes a plurality of units, such as units 710-1, 710-2, 710-3 arranged circumferentially. In some embodiments, the apparatus 700 includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 units. In some embodiments, unit 710 includes one or more features / components / devices disclosed herein (e.g., siphon valve structure 110). In some embodiments, each unit 710 includes one or more features / components / devices disclosed herein (e.g., siphon valve structure 110). In some embodiments, each unit is identical to another unit among a plurality of units. In some embodiments, at least one unit is different from the other units among a plurality of units.

[0096] Exemplary Workflow

[0097] Figures 6A to 6J These are schematic diagrams illustrating exemplary workflows according to some exemplary embodiments of the present disclosure. While a specific sample (e.g., whole blood) is used in describing the workflow, it should be noted that the present disclosure is not limited thereto. Other samples, such as those disclosed herein, may be used. Additionally, the workflow may be automated.

[0098] refer to Figure 6A The present disclosure illustrates an apparatus (e.g., a disc) 600 according to some exemplary embodiments. For clarity, only a portion of the apparatus is shown. The apparatus 600 is capable of rotating about a rotation axis (such as a vertical rotation axis 601). In some embodiments, the apparatus 600 can rotate at speeds of at least about 1000 rpm, at least about 1200 rpm, at least about 1400 rpm, at least about 1600 rpm, at least about 1800 rpm, at least about 2000 rpm, at least about 2200 rpm, at least about 2400 rpm, at least about 2600 rpm, at least about 2800 rpm, at least about 2900 rpm, at least about 3000 rpm, at least about 3500 rpm, at least about 4000 rpm, at least about 4500 rpm, at least about 5000 rpm, at least about 5500 rpm, at least about 6000 rpm, at least about 6500 rpm, or at least about 7000 rpm during one or more processes. In some implementations, during one or more processes, the device 600 may rotate at speeds of up to about 500 rpm, up to about 600 rpm, up to about 700 rpm, up to about 800 rpm, up to about 900 rpm, up to about 1000 rpm, up to about 1200 rpm, up to about 1400 rpm, up to about 1600 rpm, up to about 1800 rpm, up to about 2000 rpm, up to about 2200 rpm, up to about 2400 rpm, up to about 2600 rpm, up to about 2800 rpm, up to about 2900 rpm, up to about 3000 rpm, up to about 3500 rpm, up to about 4000 rpm, up to about 4500 rpm, or up to about 5000 rpm.

[0099] Device 600 includes one or more ports, one or more chambers, one or more channels, and one or more passages. For example, in the illustrated embodiment, device 600 includes a dilution buffer chamber 602, a sample chamber 604, a sample separation chamber 606, a sample metering chamber 608, a mixing chamber 610, a mixing / metering chamber 612, a pneumatic air and overflow chamber 614, a reporter chamber 616, a first wash buffer port 617, a wash buffer chamber 618 (also referred to as a wash buffer slow channel 618), a wash buffer fast channel 619, a delay chamber 620, a McDot lyophilization chamber 622, a siphon channel 626, a reaction (Rxn) chamber 624, a particle adjunct 628, a waste chamber 630, and an exhaust port 646. In some implementations, the Rxn chamber 624 includes or contains lyophilized reagent beads 640. In some implementations, the lyophilized reagent beads 640 include magnetic particles and antibodies. Although device 600 is illustrated to have specific components (e.g., specific chambers, passageways), it should be noted that this is merely an example and not a limitation. In some implementations, device 600 may not include one or more of these specific components. In some implementations, device 600 may include additional or alternative components, such as those disclosed herein.

[0100] Device 600 can be used to perform a variety of immunoassays. Examples of typical immunoassays that can be run in device 600 include, but are not limited to, free thyroxine (T4), thyroid-stimulating hormone (TSH), beta-diuretic natriuretic peptide (BNP) (such as N-terminal BNP precursors), C-reactive protein (CRP), vitamin D, prostate-specific antigen (PSA), ferritin, D-dimer, testosterone, and troponin, or combinations thereof, in a sample.

[0101] refer to Figure 6B The illustration depicts a sample and buffer loading process according to some exemplary embodiments of the present disclosure. In this process, a sample (e.g., whole blood) is loaded into sample chamber 604, and dilution buffer is loaded into dilution buffer chamber 602. In some embodiments, the sample is a whole blood sample. In some implementations, the buffer is a TBST dilution buffer, for example, a mixture of Tris-buffered saline (TBS) (buffer solution) and polysorbate 20 (a polysorbate-type nonionic surfactant).

[0102] refer to Figure 6CThe diagram illustrates a spin process according to some exemplary embodiments of the present disclosure. In some implementations, device 600 spins rapidly about a vertical rotation axis 601. In some implementations, a sample (e.g., a whole blood sample) moves to a sample separation chamber 606. As device 600 spins, the whole blood sample separates into plasma and cellular fractions. Dilution buffer moves to a mixing chamber 610 and a mixing / measuring chamber 612. Additionally, the dilution buffer is metered in the mixing / measuring chamber 612. If excess dilution buffer is present, the excess overflows into pneumatic air and an overflow chamber 614.

[0103] refer to Figure 6C The illustration depicts a sample initiation process according to some exemplary embodiments of the present disclosure. In some implementations, the rotation of device 600 is slowed, which allows the plasma portion of the sample to flow from sample separation chamber 606 to sample metering chamber 608. As the rotation of device 600 slows, TBST dilution buffer moves from mixing / metering chamber 612 to mixing chamber 610 due to the expansion of pneumatic air and trapped air in overflow chamber 614, thereby pushing TBST dilution buffer from mixing / metering chamber 612 into mixing chamber 610.

[0104] In some implementations, in terms of time, as the rotation of device 600 slows down, TBST dilution buffer flows from mixing / measuring chamber 612 to mixing chamber 610, and then plasma flows from sample separation chamber 606 to sample metering chamber 608. This blocks the flow of plasma to mixing chamber 610, thereby allowing plasma to be metered in sample metering chamber 608.

[0105] refer to Figure 6E-1 and Figure 6E-2 The illustration depicts a sample injection and mixing process according to some exemplary embodiments of the present disclosure. In some implementations, post-metered plasma flows from the sample metering chamber 608 to the mixing chamber 610 by increasing the rotational speed of the device 600. The post-metered plasma is mixed with TBST dilution buffer by accelerating and decelerating the rotation of the device 600, which causes the pneumatic air and the trapped air in the overflow chamber 614 to expand and contract, thereby pushing the plasma / TBST dilution buffer mixture back and forth.

[0106] refer to Figure 6F-1 and Figure 6F-2 The illustration depicts the lyophilized bead reconstruction and pull-down process according to some exemplary embodiments of the present disclosure. In some implementations, the rotational speed of device 600 is reduced. This causes the pneumatic air and the captured gas in overflow chamber 614 to expand, thereby pushing the plasma / dilution buffer mixture from mixing / metering chamber 612 and mixing chamber 610 through siphon tube 625 and into reaction (Rxn) chamber 624.

[0107] In some implementations, the magnetic particles and antibodies in the lyophilized reagent beads 640 (e.g., as...) Figure 6A (As shown) dissolves during this process.

[0108] In some implementations, additionally or depending on the situation, the ultrasonic probe (e.g., such as...) Figure 3C (As shown) it contacts the Rxn chamber 624 to mix its contents. For example, in some implementations, an ultrasonic probe is used to rapidly homogenize the reaction mixture.

[0109] and Figure 6F-1 and Figure 6F-2 Let's refer to each other. Figure 6G-1 and Figure 6G-2 The illustration depicts a cleaning process (e.g., a first cleaning) according to some exemplary embodiments of the present disclosure. In some implementations, magnetic particles 638 can be separated from particle appendage 628 by placing a magnet 636 close to particle appendage 628. In some implementations, a cleaning buffer is added to a cleaning buffer fast lane 619 and a cleaning buffer chamber 618 (also referred to as a buffer slow lane 618). The device 600 spins, causing the cleaning buffer in the cleaning buffer fast lane 619 to move to the Rxn chamber 624, bind with the diluted plasma mixture, and then move to the waste chamber 630. The cleaning buffer in the cleaning buffer slow lane 618 is held in the delay structure 620 during this period and eventually flows to the Rxn chamber 624 and the waste chamber 630. In some implementations, the magnetic particles 638 remain in particle appendage 628 during this process.

[0110] refer to Figure 6H-1 and Figure 6H-2 The illustration depicts the reporter lyophilized bead reconstruction and incubation process according to some exemplary embodiments of the present disclosure. In some implementations, a buffer solution is added to the reporter chamber 616. The device 600 spins, thereby forcing the buffer solution to flow from the reporter chamber 616 to the reporter lyophilization chamber 622, dissolving the reporter lyophilized beads 623, which then flow into the Rxn chamber 624. In some implementations, the device 600 stops spinning, and the magnetic particles 638, as shown in FIG. 6G, are resuspended in solution in the Rxn chamber 624. Figure 6H-2 As shown. In some implementations, a static magnet 636 is used to move the magnetic particles 638 back into the Rxn chamber 624, and / or an ultrasonic probe is used to achieve uniform levitation.

[0111] refer to Figure 6I-1 and Figure 6I-2The illustration depicts a particle pull-down and washing process according to some exemplary embodiments of the present disclosure. In some implementations, after incubation, a magnet 636 is used to move magnetic particles and bound reporter particles 638 into particle appendages 628. In some implementations, washing buffer is added to a washing buffer fast lane 619 and a washing buffer slow lane 618. In some implementations, the device 600 spins, causing the washing buffer in the washing buffer fast lane to move into the Rxn chamber 624, bind with the reaction mixture, and then move into the waste chamber 630. The washing buffer in the washing buffer slow lane is held in the delay structure 620 during this process and eventually flows into the Rxn chamber 624 and the waste chamber 630. In some implementations, the magnetic particles 638 remain in the particle appendages 628 during this process.

[0112] refer to Figure 6J The illustration depicts a resuspended particle and readout process according to some exemplary embodiments of the present disclosure. In some implementations, a buffer solution is added to a wash buffer chamber 618. The device 600 spins, thereby transferring the buffer solution from the wash buffer chamber 618 to the Rxn chamber 624. For example, an ultrasonic probe is used, such as... Figure 6I-1 and Figure 6I-2 The magnetic particles bound to reporter particles 638, as shown, are resuspended in Rxn chamber 624 and mixed with TBST buffer. In some implementations, the Rxn chamber 624 is then aligned below the readout sensor for result detection.

[0113] The apparatus and methods disclosed herein can be used in a variety of applications, including but not limited to clinical chemistry, immunoassays, and hematology. Examples of clinical chemistry, immunoassays, and / or hematology are disclosed in WO2018 / 119437, WO2018 / 140719, WO2022 / 029731, and WO 2022 / 029732, the contents of each of which are hereby incorporated by reference in their entirety. The apparatus and methods disclosed herein can be operated or performed by systems similar to those disclosed in U.S. Patent Application No. 17 / 371,746, the contents of which are hereby incorporated by reference in their entirety.

[0114] Description of the subject technology of the clause

[0115] For convenience, various examples of aspects of this disclosure are described with numbered clauses (1, 2, 3, etc.). These are provided by way of example only and do not limit the subject matter.

[0116] Clause 1. An apparatus comprising: a rotating shaft; an exhaust port; a siphon having a top positioned radially outside the exhaust port relative to the rotating shaft; and a ballast chamber having a first outlet connected to the exhaust port and a second outlet connected to an inlet of the siphon, wherein the first outlet of the ballast chamber is positioned radially within the second outlet of the ballast chamber and radially outside the top of the siphon relative to the rotating shaft, thereby dividing the ballast chamber into a non-ventilated ballast portion radially within the first outlet and a ventilated ballast portion radially outside the first outlet.

[0117] Clause 2. The apparatus as described in Clause 1, wherein the second outlet of the ballast chamber is formed at or near the outermost position in the radial direction of the ballast chamber.

[0118] Clause 3. The apparatus as described in any of the preceding clauses further includes: a first passage connecting the first outlet of the ballast chamber to the exhaust port.

[0119] Clause 4. The apparatus as described in any of the preceding clauses further includes: an upstream chamber connected to the ballast chamber.

[0120] Clause 5. The apparatus as described in Clause 4, wherein the ballast chamber includes an inlet located in the non-ventilated ballast portion, and the upstream chamber is connected to the inlet located in the non-ventilated ballast portion of the ballast chamber.

[0121] Clause 6. The apparatus of any one of Clauses 4 to 5, wherein: the upstream chamber includes an outlet connected to the ballast chamber; and the top of the siphon and the exhaust port are radially within the outlet of the upstream chamber.

[0122] Clause 7. The apparatus as described in Clause 6, wherein the outlet of the upstream chamber is formed at the outermost position in the radial direction of the upstream chamber.

[0123] Clause 8. The apparatus of any one of Clauses 4 to 7 further comprises: a U-shaped channel connecting the ballast chamber to the upstream chamber.

[0124] Clause 9. The apparatus as described in Clause 8, wherein the volume of the ballast chamber in the inward position from the first outlet is greater than the volume required beyond the top of the siphon.

[0125] Clause 10. The apparatus as described in any of the preceding clauses further includes: a downstream chamber connected to the outlet of the siphon tube.

[0126] Clause 11. The apparatus as described in Clause 10, wherein the downstream chamber is positioned radially outside the second outlet.

[0127] Clause 12. The apparatus as described in any of the preceding clauses, wherein the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof, is configured to allow initial loading of the fluid by rotating the apparatus at a speed that causes the fluid to fill the ballast chamber and the siphon, thereby forming a first meniscus radially within the first outlet in the ballast chamber and a second meniscus radially outside the top of the siphon in the siphon.

[0128] Clause 13. The apparatus as described in Clause 12, wherein the exhaust port, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof are configured to allow the upstream chamber to be emptied by reducing the speed.

[0129] Clause 14. The apparatus as described in Clause 12, wherein the exhaust port, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof are configured to allow the upstream chamber to be emptied by increasing the speed.

[0130] Clause 15. The apparatus of any one of Clauses 13 to 14, wherein the vent, the siphon, the ballast chamber, the first channel, the upstream chamber, the U-shaped channel, or any combination thereof are configured to allow complete evacuation of the upstream chamber.

[0131] Clause 16. An apparatus comprising: a rotating shaft; a chamber; an appendage including an inlet connected to the chamber and a trapping area radially outside the inlet relative to the rotating shaft; and magnetic particles capable of being moved between the chamber and the appendage by means of a magnet, positioning the chamber relative to the magnet, rotating the apparatus, or any combination thereof.

[0132] Clause 17. The apparatus of Clause 16, wherein the chamber includes a flexible covering layer that responds to one or more acoustic pulses to facilitate mixing of the magnetic particles with the fluid in the chamber.

[0133] Clause 18. The apparatus of any one of Clauses 16 to 17, wherein the magnetic particles are magnetic nanoparticles.

[0134] Clause 19. A method comprising: (A) placing a chamber of an apparatus near a magnet such that magnetic particles contained in the chamber form a first alignment; (B) rotating the apparatus relative to the magnet to move the magnetic particles into an appendage connected to the chamber, wherein the appendage includes an inlet and a trapping zone radially outside the inlet relative to the axis of rotation of the apparatus; and (C) rotating the apparatus at a certain speed to flush out unbound analytes or non-specifically bound particles from the chamber, wherein the magnetic particles remain in the trapping zone.

[0135] Clause 20. The method as described in Clause 19, wherein the placement is performed by rotating the device (A).

[0136] Clause 21. The method of any one of Clauses 19 to 20, wherein the magnet generates the strongest magnetic field in the middle portion of the chamber.

[0137] Clause 22. The method of any one of Clauses 19 to 21, wherein the rotation (B) is performed continuously.

[0138] Clause 23. The method of any one of Clauses 19 to 21, wherein the rotation (B) is performed intermittently.

[0139] Clause 24. The method of any one of Clauses 19 to 22, further comprising: (D) filling the chamber with fluid after the rotation (C); and (E) rotating the device relative to the magnet to move the magnetic particles from the appendage to the chamber.

[0140] Clause 25. The method as described in Clause 24, wherein the rotation (E) is performed continuously.

[0141] Clause 26. The method as described in Clause 24, wherein the rotation (E) is performed intermittently.

[0142] Clause 27. The method of any one of Clauses 19 to 26, wherein the chamber comprises a flexible covering layer, the method further comprising: (F) aligning the chamber with an ultrasonic probe; (G) moving the ultrasonic probe or the device such that the ultrasonic probe contacts the flexible covering layer; and (H) activating the ultrasonic probe to emit one or more pulses to facilitate mixing of the magnetic particles with the fluid.

[0143] Clause 28. The method as described in Clause 27, wherein the alignment (F) is achieved by rotating the device.

[0144] Clause 29. The method of any one of Clauses 27 to 28, wherein the alignment (F), the movement (G), and the activation (H) are performed prior to the placement (A).

[0145] Clause 30. The method of any one of Clauses 27 to 28, wherein the alignment (F), the movement (G), and the activation (H) are performed after the rotation (E).

[0146] Clause 31. The method of any one of Clauses 27 to 30, further comprising: (I) allowing the mixture in the chamber to incubate for a period of time after the activation (H).

[0147] Clause 32. A device for operating any of the foregoing clauses or a system for performing any of the foregoing clauses.

[0148] Cited terms and references

[0149] The terminology used herein is for the purpose of describing a particular implementation only and is not intended to limit the claims. As used in the description of the implementation and in the appended claims, the singular forms “a(a)”, “an”, and “described” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be understood that terms such as “left” or “right,” “top” or “bottom,” “lower” or “upper,” “inner” or “outer,” “inward” or “outward” are used to describe features of exemplary embodiments with reference to the location of features shown in the accompanying drawings. It will be understood that although the terms “first,” “second,” etc., may be used herein to describe various elements, these elements should not be limited by these terms. These terms are used only to distinguish one element from another. For example, a first element may be referred to as a second element, and similarly, a second element may be referred to as a first element, without changing the meaning of the description, provided that the renaming of “first element” and “second element” is consistent.

[0150] As used herein, the term “and / or” refers to and covers any and all possible combinations of one or more of the associated listed items. It will also be understood that the terms “include, include, including, comprise, comprises, and / or comprising”, when used in this specification, specify the presence of the stated feature, integer, step, operation, element, and / or component, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0151] The term “about” or “approximately” is used herein to provide textual support for precise figures that follow it, as well as figures that are close to or approximate to the figures that follow the term. In determining whether a figure is close to or approximates a specifically listed figure, a figure that is close to or approximates an unlisted figure may be a figure that is substantially equal to a specifically listed figure in the context in which it is presented. It should be understood that all numerical values ​​and ranges disclosed herein are approximate values ​​and ranges, whether or not “about” is used with them. It should also be understood that the term “about” as used herein in conjunction with figures refers to a value that can be ±0.01% (inclusive), ±0.1% (inclusive), ±0.5% (inclusive), ±1% (inclusive), ±2% (inclusive), ±3% (inclusive), ±5% (inclusive), ±10% (inclusive), or ±15% (inclusive) of the figure. It should also be understood that when a numerical range is disclosed herein, any numerical value falling within that range is also specifically disclosed.

[0152] As used herein, the term "if" is interpreted as meaning "when," "after," "in response to a determination," "in response to a detection," or "according to a judgment," depending on the context. Similarly, as used herein, the terms "if a determination" or "if [the condition or event] is detected" are interpreted as meaning "after a determination," "in response to a determination," "after the detection of [the condition or event]," "in response to the detection of [the condition or event]," or "according to a determination based on the detection of [the condition or event]," depending on the context.

[0153] When a reference number contains the symbol "i", the reference number refers to a general component, assembly, or implementation. For example, "unit i" refers to the i-th unit among a plurality of units.

[0154] All references cited in this paper are incorporated herein by reference in their entirety and for all purposes, as if each individual announcement, patent, or patent application were specifically and individually indicated to be incorporated herein by reference in their entirety for all purposes.

Claims

1. An apparatus comprising: Rotation axis; Exhaust port; A siphon tube having a top, the top being positioned radially relative to the axis of rotation outside any portion of the exhaust port or the channel connected to the exhaust port; as well as A ballast chamber having a first outlet connected to the exhaust port and a second outlet connected to the inlet of the siphon pipe. The first outlet of the ballast chamber is positioned radially within the second outlet of the ballast chamber and radially outside the top of the siphon relative to the axis of rotation, thereby dividing the ballast chamber into a non-ventilated ballast portion radially within the first outlet and a ventilated portion radially outside the first outlet.

2. The apparatus of claim 1, wherein the second outlet of the ballast chamber is formed at or near the outermost position in the radial direction of the ballast chamber.

3. The apparatus of claim 1, further comprising: A first channel connects the first outlet of the ballast chamber to the exhaust port.

4. The apparatus of claim 1, further comprising: An upstream chamber, which is connected to the ballast chamber.

5. The apparatus of claim 4, wherein the ballast chamber includes an inlet located in the non-ventilated ballast portion, and the upstream chamber is connected to the inlet located in the non-ventilated ballast portion of the ballast chamber.

6. The apparatus of claim 4, wherein: The upstream chamber includes an outlet connected to the ballast chamber; and Depending on the situation, the top of the siphon and the exhaust port are radially located within the outlet of the upstream chamber.

7. The apparatus of claim 6, wherein the outlet of the upstream chamber is formed at the outermost position in the radial direction of the upstream chamber.

8. The apparatus of claim 4, further comprising: A U-shaped passage connects the ballast chamber to the upstream chamber.

9. The apparatus of claim 8, wherein the volume of the ballast chamber in the inward position of the first outlet is greater than the volume required beyond the top of the siphon.

10. The apparatus of claim 1, further comprising: Downstream chamber, which is connected to the outlet of the siphon tube.

11. The apparatus of claim 10, wherein the downstream chamber is positioned radially outside the second outlet.

12. An apparatus comprising: Rotation axis; room; An accessory comprising an inlet connected to the chamber and a capture zone radially outside the inlet relative to the axis of rotation; as well as Magnetic particles, which are capable of moving between the chamber and the appendage via a magnet, positioning the chamber relative to the magnet, rotating the device, or any combination thereof.

13. The apparatus of claim 12, wherein the chamber includes a flexible covering layer that responds to one or more mechanical pulses to facilitate mixing of the magnetic particles with the fluid in the chamber.

14. The apparatus of claim 13, wherein the mechanical pulse is generated using an ultrasonic probe in contact with the cover layer.

15. The apparatus of claim 12, wherein the magnetic particles are magnetic nanoparticles.

16. A method comprising: (A) The chamber of the device is placed near a magnet such that the magnetic particles contained in the chamber form a first arrangement; (B) Rotating the device relative to the magnet to move the magnetic particles into an appendage connected to the chamber, wherein the appendage includes an inlet and a trapping area radially outside the inlet relative to the axis of rotation of the device; and (C) The device is rotated at a certain speed to flush out unbound analytes or non-specifically bound particles from the chamber, wherein the magnetic particles and the residual liquid volume remain in the capture zone.

17. The method of claim 16, wherein the placement (A) is performed by rotating the device.

18. The method of claim 16, further comprising: (D) After the rotation (C), the chamber is filled with fluid; as well as (E) Rotate the device relative to the magnet to move the magnetic particles from the appendage to the chamber.

19. The method of claim 18, wherein the chamber comprises a flexible covering layer, the method further comprising: (F) Align the chamber with the ultrasonic probe; (G) Move the ultrasonic probe or the device so that the ultrasonic probe comes into contact with the flexible covering layer; and (H) Activate the ultrasonic probe to emit one or more pulses to promote the mixing of the magnetic particles with the fluid.

20. The method of claim 19, wherein the alignment (F) is achieved by rotating the device.

21. The method of claim 20, further comprising: (I) After the activation (H), the mixture in the chamber is allowed to incubate for a period of time.

22. The method of claim 16, wherein the chamber comprises a flexible covering layer, the method further comprising: (D) After the rotation (C), the chamber is filled with fluid; as well as (E) Align the chamber with the ultrasonic probe; (F) Move the ultrasonic probe or the device so that the ultrasonic probe comes into contact with the flexible cover layer; and (G) Activate the ultrasonic probe to emit one or more pulses to facilitate the removal of magnetic particles from the capture zone and the mixing of the magnetic particles with the fluid.

23. The method of claim 22, wherein the alignment (G) is achieved by rotating the device.

24. The method of claim 22, further comprising: (H) After the activation (G), the mixture in the chamber is allowed to incubate for a period of time.

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