Pneumatic siphon valve and reaction chamber for sample analysis

Abstract

The rotatable device includes a vent port, a siphon, and a ballast chamber. The siphon has a top positioned radially outward from the vent port with respect to the axis of rotation. The ballast chamber has a first outlet connected to the vent port and a second outlet connected to the siphon inlet. The first outlet of the ballast chamber is positioned radially inward from the second outlet of the ballast chamber with respect to the axis of rotation, and radially outward from the top of the siphon. In this way, the first outlet of the ballast chamber divides the ballast chamber into an unventilated ballast portion radially inward from the first outlet and an aerated ballast portion radially outward from the first outlet, thereby isolating pressure changes within the ballast chamber from the radial position of the siphon inlet in the ballast chamber.

Description

Technical Field

[0004] , ,

[0001] Cross - Reference to Related Applications This application claims priority to U.S. Provisional Patent Application No. 63 / 489,420, filed Mar. 9, 2023, and U.S. Provisional Patent Application No. 63 / 489,667, filed Mar. 10, 2023. The disclosure of each application is hereby incorporated by reference in its entirety for all purposes.

[0002] This disclosure relates to devices and methods for directing fluids, mixing fluids, and / or resuspending reagents in centrifugal microfluidic technology.

Background Art

[0003] Currently, 70% of all medical decision - making depends on laboratory diagnosis, but today's diagnostic process is far removed from the way medical care is provided. In primary healthcare systems, patients need to go to an external blood collection facility for blood sampling. The blood collected there is sent to a laboratory via a transporter and processed the next day. This means that the test results are communicated to medical experts some time after the patient has been discharged. This friction between medical care provision and disease management leads to significant waste in the healthcare system as follows. a. Patients often delay undergoing tests or do not follow the recommendations for tests and subsequent treatments. b. Gaps in the diagnostic process lead to missed tests, overlooked diagnoses, lack of intervention, and ultimately worsen the prognosis. c. Medical experts waste time matching test orders with patient examination records. When intervention is required, more time is wasted contacting the patient and progressing to the next step in the patient's treatment pathway.

[0004] These problems are even more acute when caring for local residents and patients belonging to groups disadvantaged by the social determinants of health. This is because there are many challenges in successfully following up on the initial diagnosis.

[0005] Several companies have developed point-of-care (POCT) instruments to bridge this gap. However, these instruments are limited to a single type of test and cannot fully meet the workflow needs of primary care providers for a single system that produces simple, comprehensive, and rapid test results. A product that addresses these needs is currently under development. This product achieves this objective through a highly automated workflow using centrifugal microfluidic disks.

[0006] Centrifugal microfluidic technology is used in clinical chemistry, immunoassays, hematology, medicine, biomedical research, and other fields. Many of these applications utilize a non-aeration chamber connected to a siphon flow path that acts as a pneumatically controlled valve. However, the pressure changes of such valves depend on the radial position of the siphon inlet in the chamber. Furthermore, many of these applications require stopping the cartridge during the execution of a specific workflow to accommodate multiple cleaning requirements. However, existing valve designs such as conventional pneumatic siphons, simple siphon measuring valves, and capillary siphon valves are not satisfactory for these applications.

[0007] Therefore, improvements in devices and methods in centrifugal microfluidics technology are desired. [Overview of the project]

[0008] This disclosure addresses these and other problems in the art by providing: (i) a siphon valve structure that isolates pressure changes within the chamber from the radial position of the siphon inlet in the chamber and / or reduces the space occupied on the cartridge; (ii) a reusable siphon valve structure that is independent of residual fluid; and (iii) a centrifugal device and method that not only retains magnetic particles while washing away all unwanted components from the reaction chamber, but also returns these particles to the main reaction chamber to enable homogenization of the mixture.

[0009] In one embodiment, the disclosure provides a device rotatable about a rotation axis. The device includes a vent port, a siphon, a ballast chamber, and / or other components disclosed herein (e.g., a U-shaped channel described later) for introducing liquid into the ballast chamber without allowing air to escape from the ballast chamber. The siphon has a top positioned radially outward from the vent port with respect to the rotation axis. The ballast chamber has a first outlet connected to the vent port and a second outlet connected to the inlet of the siphon. The first outlet of the ballast chamber is positioned radially inward from the second outlet of the ballast chamber and radially outward from the top of the siphon with respect to the rotation axis, thereby dividing the ballast chamber into an unventilated ballast portion radially inward from the first outlet and an aerated ballast portion radially outward from 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.

[0010] In some embodiments, the device further comprises a first flow path connecting a first outlet of a ballast chamber to a ventilation port, an upstream chamber connected to the ballast chamber, a U-shaped flow path connecting the ballast chamber to the upstream chamber, a downstream chamber connected to the outlet of a siphon, or any combination thereof.

[0011] In some embodiments, the ballast chamber includes an inlet in a non-ventilated ballast portion, and the upstream chamber is connected to the inlet in the non-ventilated ballast portion 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 ventilation port are radially inward from the outlet of the upstream chamber. In some such embodiments, the outlet of the upstream chamber is formed at the radially outermost position of the upstream chamber.

[0012] In some embodiments, the volume within the ballast chamber between the radial position of the first outlet and the radial position of the second outlet is greater than the volume required to clear the top of the siphon. In some embodiments, the downstream chamber is positioned radially outward from the ballast chamber.

[0013] In some embodiments, a vent port, a siphon, a ballast chamber, a first flow path, an upstream chamber, a U-shaped flow path, or any combination thereof, is configured to allow initial fluid filling by rotating the device at a speed that fills the ballast chamber and siphon with fluid, thereby forming a first meniscus inside the ballast chamber radially inward of the first outlet and a second meniscus inside the siphon radially outward of the top of the siphon.

[0014] In some embodiments, the vent port, siphon, ballast chamber, first channel, upstream chamber, U-shaped channel, or any combination thereof is configured to allow discharge from the upstream chamber by reducing the velocity. Alternatively, in some embodiments, the vent port, siphon, ballast chamber, first channel, upstream chamber, U-shaped channel, or any combination thereof is configured to allow discharge from the upstream chamber by increasing the velocity.

[0015] In some embodiments, a vent port, siphon, ballast chamber, first flow path, upstream chamber, U-shaped flow path, or any combination thereof is configured to allow complete discharge from the upstream chamber.

[0016] In another embodiment, the disclosure provides a device rotatable about a rotation axis. The device includes a chamber, an attachment, and magnetic particles. The attachment includes an inlet connected to the chamber and a capture zone located radially outward from the inlet with respect to the rotation axis. The magnetic particles are movable between the chamber and the attachment by a magnet, positioning of the chamber relative to the magnet, rotation of the device, or any combination thereof.

[0017] In some embodiments, the chamber includes a flexible capping layer that facilitates mixing of magnetic particles with the fluid within the chamber in response to one or more ultrasonic pulses. In some embodiments, the magnetic particles are magnetic nanoparticles.

[0018] In a further embodiment, the Disclosure provides a method comprising (A) positioning the chamber of a device adjacent to a magnet such that magnetic particles contained within the chamber form a first arrangement. The device comprises an attachment having an inlet connected to the chamber and a capture zone radially outward from the inlet with respect to the rotation axis of the device. The method also comprises (B) rotating the device in a first direction with respect to the magnet to move magnetic particles into the attachment connected to the chamber. The method further comprises (C) rotating the device at a rate that washes away unbound specimens or nonspecifically bound particles from the chamber. By rotating (C), the magnetic particles move into and remain in the capture zone.

[0019] In some embodiments, positioning (A) is performed by rotating the device. In some embodiments, the magnet generates the strongest magnetic field in the central part of the chamber. In some embodiments, rotation (B) is performed continuously. Alternatively, in some embodiments, rotation (B) is performed intermittently.

[0020] In some embodiments, the method further includes (D) filling the chamber with fluid following rotation (C), and (E) rotating the device in a second direction relative to the magnet to move magnetic particles from the attachment into the chamber. In some embodiments, rotation (E) is performed continuously. Alternatively, in some embodiments, rotation (E) is performed intermittently.

[0021] In some embodiments in which the chamber includes a flexible capping layer, the method further includes (F) aligning the chamber with an ultrasonic probe, (G) moving the ultrasonic probe or device so that the ultrasonic probe is in contact with the flexible capping layer, and (H) initiating the ultrasonic probe to deliver one or more pulses to facilitate mixing of magnetic particles and a fluid.

[0022] In some embodiments, alignment (F) is achieved by rotating the device. In some embodiments, alignment (F), movement (G), and activation (H) are performed before positioning (A). In some embodiments, alignment (F), movement (G), and activation (H) are performed after rotation (E).

[0023] In some embodiments, the method further includes (I) incubating the mixture in the chamber for a certain period of time after initiating (H).

[0024] The devices, systems, and methods of the present disclosure will be apparent from the accompanying drawings incorporated herein and the following detailed description of the invention, or will be shown in other features and advantages which are more particularly shown, and these serve to explain together the specific principles of the exemplary embodiments of the present disclosure.

[0025] The accompanying drawings, which are incorporated herein and constitute a part hereof, illustrate one or more exemplary embodiments of the present disclosure and, together with the detailed description, serve to explain the principles and implementations of the exemplary embodiments of the invention. The accompanying drawings are not necessarily to scale. For example, specific design features of the invention as disclosed herein, including specific dimensions, orientations, positions, and shapes, are determined in part by the particular intended use and operating environment. Further, the components shown in the figures can be usefully combined in any number and combination.

Brief Description of the Drawings

[0026] [Figure 1A] It is a schematic diagram for explaining a device according to some exemplary embodiments of the present disclosure. <000009A> [Figure 1B] It is a schematic diagram for explaining the siphon valve structure of the device of FIG. 1A according to some exemplary embodiments of the present disclosure. [Figure 1C] It is a schematic diagram for explaining the siphon valve structure of the device of FIG. 1A according to some exemplary embodiments of the present disclosure. [Figure 2A] It is a schematic diagram for explaining the operation process of using the device of FIG. 1A according to some exemplary embodiments of the present disclosure. [Figure 2B] It is a schematic diagram for explaining a device according to an alternative exemplary embodiment of the present disclosure. [Figure 2C] It is a schematic diagram for explaining a device according to a further alternative exemplary embodiment of the present disclosure. <00A01A1> [Figure 2D] It is a schematic diagram for explaining a device according to some exemplary embodiments of the present disclosure, showing the liquid during the initial filling step. [Figure 2E]Figure 2D is a schematic diagram illustrating a device according to some exemplary embodiments of the present disclosure, showing a liquid in a steady state at an initial rotational speed. [Figure 2F] Figure 2D is a schematic diagram illustrating the device according to some exemplary embodiments of the present disclosure, showing the liquid during the pretreatment step. [Figure 2G] Figure 2D is a schematic diagram illustrating the device according to some exemplary embodiments of the present disclosure, showing the liquid during the discharge step. [Figure 3A] These are images showing devices according to some exemplary embodiments of the present disclosure. [Figure 3B] This is a magnified view of a portion of Figure 3A. [Figure 3C] This is a schematic diagram illustrating some components of the device shown in Figure 3A according to some exemplary embodiments of the present disclosure. [Figure 4] This is a flowchart illustrating a method according to some exemplary embodiments of the present disclosure. [Figure 5A] This is an image illustrating a process collectively performed using the device shown in Figure 4A according to some exemplary embodiments of the present disclosure. [Figure 5B] This is an image illustrating a process collectively performed using the device shown in Figure 4A according to some exemplary embodiments of the present disclosure. [Figure 5C] This is an image illustrating a process collectively performed using the device shown in Figure 4A according to some exemplary embodiments of the present disclosure. [Figure 5D] This is an image illustrating a process collectively performed using the device shown in Figure 4A according to some exemplary embodiments of the present disclosure. [Figure 6A] This is a schematic diagram illustrating a device (e.g., a disk) according to some exemplary embodiments of the present disclosure. [Figure 6B] This is a schematic diagram illustrating a loading process according to some exemplary embodiments of the present disclosure. [Figure 6C] This is a schematic diagram illustrating a spin process according to some exemplary embodiments of the present disclosure. [Figure 6D] This is a schematic diagram illustrating a pretreatment process according to some exemplary embodiments of the present disclosure. [Figure 6E-1] This is a schematic diagram illustrating the injection and mixing processes according to some exemplary embodiments of the present disclosure. [Figure 6E-2] This is a magnified view of a portion of Figure 6E-1. [Figure 6F-1] This is a schematic diagram illustrating the re-dissolution and pull-down process of freeze-dried beads according to some exemplary embodiments of the present disclosure. [Figure 6F-2] This is a magnified view of a portion of Figure 6F-1. [Figure 6G-1] This is a schematic diagram illustrating a cleaning process according to some exemplary embodiments of the present disclosure. [Figure 6G-2] This is a magnified view of a portion of Figure 6G-1. [Figure 6H-1] This is a schematic diagram illustrating the re-dissolution and incubation process of reporter freeze-dried beads according to some exemplary embodiments of the present disclosure. [Figure 6H-2] This is a magnified view of a portion of Figure 6H-1. [Figure 6I-1] This is a schematic diagram illustrating particle pull-down and washing processes according to some exemplary embodiments of the present disclosure. [Figure 6I-2] This is a magnified view of a portion of Figure 6I-1. [Figure 6J] This is a schematic diagram illustrating the resuspended particles and reading process according to some exemplary embodiments of the present disclosure. [Figure 7] This is a schematic diagram illustrating a device (e.g., a disk) according to an alternative exemplary embodiment of the present disclosure. [Modes for carrying out the invention]

[0027] Volume-controlled pneumatic siphon valve In microfluidic technology, many applications utilize a non-aeration chamber connected to a siphon flow path that functions as a pneumatically dependent valve. However, pressure changes in such valves depend on the radial position of the siphon inlet in the chamber. Furthermore, such valves may require a relatively large space on the cartridge to function properly. This disclosure addresses these and / or other challenges by providing a siphon valve structure that decouples pressure changes within the chamber from the radial position of the siphon inlet in the chamber and / or reduces the space required on the cartridge.

[0028] Referring to the drawings, Figure 1A shows an exemplary device 100 with an exemplary siphon valve structure 110 according to several embodiments of the present disclosure, where the same reference numerals indicate the same components throughout the figure. The device 100 may be a microfluidic disk, cartridge, etc., for handling or processing a sample. In various embodiments, the device 100 is rotatable about a rotation axis 102.

[0029] The siphon valve structure 110 generally includes a vent port 120, a siphon 130, and a ballast chamber 140. The siphon has a top 132 located radially outward from the vent port with respect to the rotation axis of the device. The ballast chamber has a first outlet 142 connected to the vent port and a second outlet 143 connected to the siphon, for example, the inlet of the siphon. The first outlet 142 of the ballast chamber is located radially inward from the second outlet 143, but radially outward from the top 132 of the siphon. Thus, the first outlet 142 divides the ballast chamber into a first portion 146 and a second portion 148. The first portion 146 is located radially outward from the first outlet 142, and the second portion 148 is located radially inward from this outlet.

[0030] Because of the presence of ventilation ports, the position of the fluid meniscus does not affect the pressure in the ballast chamber when it is in the first part of the ballast chamber, as shown in Figure 1B. Thus, the first part 146 is referred to herein as the vented ballast section. However, as shown in Figure 1C, the fluid blocks the air passage to the ventilation ports, so when it is in the second part, the position of the fluid meniscus affects the pressure in the ballast chamber. Thus, the second part 148 is referred herein as the non-vented section. Since the first outlet 142 is radially inward of the second outlet 143, changes in pressure in the ballast chamber are independent of the position of the second outlet 143, which defines the radial position of the siphon inlet. This isolates the pressure changes inside the ballast chamber from the radial position of the siphon inlet.

[0031] The first and second outlets of the ballast chamber may be formed at any suitable location, as long as the radial position of the first outlet 142 of the ballast chamber is between the second outlet 143 and the top of the siphon 132. As a non-limiting example, Figure 1 shows that the second outlet 143 of the ballast chamber is formed at or near the radially outermost position of the ballast chamber.

[0032] The device 100 or siphon valve structure 110 may include additional, optional, or alternative components. For example, in some embodiments, the device 100 or siphon valve structure 110 comprises a flow path 150 connecting a first outlet of a ballast chamber to a vent port, an upstream chamber 160 connected to the ballast chamber, a U-shaped flow path 170 connecting the ballast chamber to the upstream chamber, a downstream chamber 180 connected to the outlet of a siphon, or any combination thereof. In some embodiments, the U-shaped flow path 170 may have an outward segment and an inward segment, as shown in Figures 1A to 1C and / or other figures disclosed herein.

[0033] In some embodiments, the ballast chamber includes an inlet 141 in the non-ventilated ballast portion, 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 ventilation port are radially inward from the outlet of the upstream chamber. In some embodiments, the downstream chamber is positioned radially outward from the ballast chamber. In some embodiments, the ballast chamber and the U-shaped channel are configured such that the volume inside the ballast chamber located inward from the first outlet 142 is greater than the volume required to pass over the top of the siphon, and in some embodiments, it may be greater than the volume of the U-shaped channel.

[0034] In some embodiments, the vent port, siphon, ballast chamber, first channel, upstream chamber, U-shaped channel, or any combination thereof is configured to allow initial fluid introduction by filling the ballast chamber and siphon with fluid and rotating the device at a speed that causes a first meniscus inside the ballast chamber radially inward of the first outlet 142 and a second meniscus inside the siphon radially outward of the siphon top 132. In some exemplary embodiments, the vent port, siphon, ballast chamber, first channel, upstream chamber, U-shaped channel, or any combination thereof is configured to allow discharge from the upstream chamber by changing (e.g., decreasing or increasing) the rotational speed. In some embodiments, the vent port, siphon, ballast chamber, first channel, upstream chamber, U-shaped channel, or any combination thereof is configured to allow complete discharge from the upstream chamber by changing the rotational speed.

[0035] For example, while rotating at the initial rotational speed, the ballast chamber is filled with liquid until the air pressure inside the ballast chamber matches the available centrifugal force, as shown in Figure 2A. The liquid level position 144 inside the ballast chamber is determined by various factors, including the rotational speed, the liquid level position above the upstream chamber 145, the radial position 146 of the outlet of the U-shaped flow path, the air pressure inside the chamber, the shape 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 finely tuned so that the liquid meniscus position on the siphon is radially outward from the apex 132. This blocks the flow of liquid, and the structure functions as a valve in the closed position. By changing the rotational speed, the combined action of the air pressure inside the ballast chamber and centrifugal force pushes the liquid over the apex of the siphon and into the siphon outlet, and then discharges the liquid volume into the downstream chamber. This "opens" the valve. The air pressure increases only after the liquid has filled the vent inlet (corresponding to the first outlet 142 of the ballast chamber) and not the siphon inlet (corresponding to the second outlet 143 of the ballast chamber), thus making it possible to separate the total volume to be discharged from the volume used to generate air pressure within the ballast chamber.

[0036] In some embodiments, the vent port, siphon, ballast chamber, first flow path, upstream chamber, U-shaped flow path, or any combination thereof, is configured to allow discharge from the upstream chamber by reducing the speed. For example, as a non-limiting example, Figure 2A shows an embodiment that allows discharge when the speed is reduced after the initial rotation step (e.g., a pre-treatment speed lower than the initial speed). In a particular embodiment, the initial rotation speed may be about 2900 rpm and the pre-treatment speed may be about 2500 rpm. The radius 145 of the liquid meniscus of the upstream chamber may be about 13.2 mm, the inlet radius 146 of the main chamber may be about 19 mm, the volume of the non-vent portion of the main chamber 140 may be about 6 μL, the radius of the top 132 of the siphon may be about 13 mm, the ballast chamber 140 may have a width of about 1.2 mm and a depth of about 0.6 mm, and the radius of the first outlet 142 of the main chamber may be about 20.5 mm.

[0037] In some embodiments, the vent port, siphon, ballast chamber, first flow path, upstream chamber, U-shaped flow path, or any combination thereof, is configured to allow discharge from the upstream chamber by increasing the speed. For example, as a non-limiting example, Figure 2B shows an embodiment that allows discharge when the speed is increased after the initial rotation step (e.g., a pre-treatment speed higher than the initial speed). In a particular embodiment, the initial rotation speed may be about 3000 rpm and the pre-treatment speed may be about 4300 rpm. During the initial rotation speed, the radius 145 of the liquid meniscus of the upstream chamber may be about 16 mm, the radius 146 of the inlet of the main chamber may be about 19 mm, the volume of the non-vent portion of the main chamber 140 may be about 6 μL, the radius of the top 132 of the siphon may be about 16.5 mm, the width of the ballast chamber 140 may be about 1.2 mm and the depth may be about 0.6 mm, and the radius of the first outlet 142 of the main chamber may be about 20.5 mm. After accelerating to a higher pre-processing speed, the liquid meniscus on the upstream chamber moves outward to position 148, and the liquid meniscus radius in the main ballast moves inward to position 147. This causes the liquid meniscus position in the siphon flow path to move inward beyond the siphon top 132, which then causes the liquid volume to be discharged into the downstream chamber, thereby "opening" the valve.

[0038] As a further non-limiting embodiment, Figure 2C shows an embodiment in which some components of the device differ in shape or position from those in Figures 2A and 2C. In certain embodiments, the initial rotational speed may be about 3500 rpm, and the pre-treatment speed may be about 3100 rpm. The radius 145 of the liquid meniscus of the upstream chamber may be about 27.5 mm, the inlet radius 146 of the main chamber may be about 36 mm, the volume of the non-ventilated portion of the main chamber 140 may be about 1.8 μL, the radius of the top 132 of the siphon may be about 31 mm, the ballast chamber may have a width of about 1.3 mm and a depth of about 0.8 mm, and the R start ballast may be about 41 mm.

[0039] Referring to Figures 2D to 2G, the position of the liquid in a device with an operating siphon valve structure 110 according to several embodiments of the present disclosure is shown. Figure 2D shows the liquid during the initial injection step. Figure 2E shows the liquid at a steady state of the initial rotational speed. Figure 2F shows the liquid during the pretreatment step. Figure 2G shows the liquid during the discharge step.

[0040] Figures 2A, 2B, and 2C show components with specific shapes, and the corresponding paragraphs provide specific values ​​for some configuration / operation parameters; however, these are illustrative examples only, and the present invention is not limited to these. The device and / or siphon valve structure may consist of additional, optional, or alternative components that may have different shapes and / or sizes, be positioned in different locations, and operate at different speeds.

[0041] The siphon valve structure of this disclosure offers several advantages. It provides greater design flexibility and allows for a more compact structure. This is particularly effective when the volume required for pneumatic control is smaller than the volume that needs to be extracted from the ballast chamber. It also offers size advantages, as a small air chamber compressing a small volume can generate high pressure despite extracting a large volume of fluid. Furthermore, multiple chambers can operate at the same speed / volume despite different discharge volumes. This allows for higher pressures and a wider operating speed range. Additionally, it enables the incorporation of more functionality into a device (e.g., a disk or cartridge), allowing it to perform more operations and / or be fine-tuned to meet desired workflow requirements.

[0042] Volume-independent, reusable pneumatic siphon valve Many applications, such as immunoassays using centrifugal force-sensitive particles and processes involving reactions that benefit from multiple washing steps, often require stopping cartridges during specific workflow steps. However, existing valve designs, such as conventional pneumatic siphons, simple siphon measuring valves, and capillary siphon valves, are unsatisfactory for these applications. For example, conventional pneumatic siphons are difficult to operate again at the same operating speed after initial discharge and stopping. This is because there is usually some residual volume remaining inside the U-shaped flow path and chamber, which flows into the main chamber when the speed is increased. Because of the remaining liquid, the volume of the compressed air chamber is not as clearly defined as in the initial state, and the reliability of conventional pneumatic siphons decreases after initial use. Simple siphon measuring valves merely 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 pre-treat the siphon. Because capillaries depend on their surface properties, capillary siphon valves are susceptible to the effects of the liquid being processed and the manufacturing method used to create the valve. These may also have different operating ranges after being wetted with different liquids.

[0043] This disclosure addresses these and / or other challenges by providing a reusable siphon valve structure that is independent of the remaining fluid. The structure has a hybrid valve setup that enables continuous fluid delivery while maintaining a more compact single measuring structure with a high level of control and / or precision.

[0044] The general concept of a reusable siphon valve structure is similar to or identical to the siphon valve structure 110 disclosed herein. Since the ballast chamber 140 is connected to the vent port 120, the ballast chamber is divided into two parts, one vented and the other non-vented. Thus, as long as the remaining fluid meniscus remains within the vented portion (e.g., as long as it does not exceed the radial position of the first outlet 142), the remaining liquid does not affect the pressure inside the ballast chamber. This allows for independent control of the pressure inside the chamber and enables the reuse of the siphon valve structure with a high level of control and / or precision, even when liquid remains.

[0045] In some embodiments, as schematically shown in Figure 2C, 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 siphon inlet) is located at the radially outermost position of the ballast chamber, and the volume inside the ballast chamber from the outlet 142 is greater than the volume required to clear the top of the siphon, and in some embodiments, it may be greater than the volume of the U-shaped channel. This allows for multiple reuses of the same valve structure and is therefore much more efficient in terms of cartridge space for the same volume.

[0046] In some embodiments, the operating speed is finely tuned to ensure complete discharge from the upstream chamber. For example, in some embodiments, 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 discharge from one or more chambers, slowing down or stopping the rotation as needed, and repeating these steps an optional number of times.

[0047] Effective and efficient magnetic particle reaction chamber Magnetic particles, when properly functionalized, can be used as components for reactions. They are useful when unbound reagents and sample interfering substances need to be washed away from specifically bound samples or reporters. When such reactions are carried out using a centrifugal device, these particles need to be retained while unwanted components are washed away. In the case of centrifugal devices that do not have any active magnetic elements, an external magnetic field is required to retain the magnetic particles while washing away unwanted components. If the external magnetic field does not follow the rotational motion of the centrifugal device for washing purposes, a specific mechanism is required in the device to retain the magnetic particles. This mechanism must allow both the retention and release of the magnetic particles when needed. Another challenge in reactions using magnetic particles is that the magnetic particles need to be redispersed / homogenized in the solution in order to obtain an efficient reaction rate.

[0048] This disclosure addresses these and / or other issues by providing a centrifugal device and method that can not only retain magnetic particles when washing away all unwanted components from the reaction chamber, but also return these particles to the main reaction chamber to homogenize the mixture.

[0049] Referring to Figures 3A to 3C, exemplary devices 300 according to several embodiments of the present disclosure are shown. The device is rotatable about a rotation axis 302. The device 300 includes a chamber 310, an attachment 320, and magnetic particles 330. The attachment 320 includes an inlet 322 connected to the chamber 310 and a capture zone 324 located radially outward from the inlet with respect to the rotation axis. When the device is fabricated, the magnetic particles are provided in the chamber or attachment. The chamber and attachment are configured such that the magnetic particles are movable between the chamber and the attachment by a magnet, positioning of the chamber relative to the magnet, rotation of the device, or any combination thereof. In some embodiments, the magnetic particles are magnetic nanoparticles.

[0050] In some embodiments, the chamber 310 includes a flexible capping layer 312, where, for example, one of the chamber walls is made of a flexible material. The flexible capping layer responds to one or more ultrasonic pulses to facilitate mixing of magnetic particles with the fluid in the chamber. This makes it possible to rapidly homogenize the reaction mixture without adding additional mechanisms and / or reaction volume, for example, by using an ultrasonic probe.

[0051] Referring to Figure 4, a flowchart is shown illustrating exemplary methods 400 for mixing fluids according to several embodiments of the present disclosure. In the flowchart, preferred parts of the method are indicated by solid lines, while additional, optional, or alternative parts of the method are indicated by dashed lines. The processes disclosed herein and illustrated in the flowchart may, but may not, be performed in the order presented, or in their entirety.

[0052] Referring to block 402, in some embodiments, the method includes (A) positioning the chamber of the device adjacent to the magnet such that the magnetic particles contained within the chamber form a first arrangement. For example, in some embodiments, the method includes positioning the chamber 310 of the device 300 adjacent to the magnet, as shown in Figure 5A. In some embodiments, positioning (A) is carried out by rotating the device. Alternatively, in some exemplary embodiments, positioning (A) is carried out by moving the magnet, or by moving the magnet and the device. In some embodiments, the magnet generates the strongest magnetic field in the central portion of the chamber.

[0053] Referring to block 404, in some embodiments, the method also includes (B) rotating the device in a first direction relative to the magnet to move magnetic particles into an attachment connected to a chamber, the attachment including an entrance and a capture zone radially outward from the entrance with respect to the rotation axis of the device. For example, as shown in Figures 5B and 5C, as the device rotates relative to the magnet, magnetic particles move from the chamber 310 into the attachment 320 connected to the chamber. The rotation of the device can be performed continuously (e.g., smoothly rotating from one position to another without stopping) or intermittently (e.g., in a series of angular positions).

[0054] Referring to block 406, in some embodiments, the method further includes (C) rotating the device at a rate that washes away unbound specimens or nonspecifically bound particles from the chamber, while the magnetic particles remain within the capture zone. For example, in Figures 5C and 5D, when the device is rotated at a rate that washes away unbound specimens or nonspecifically bound particles from the chamber, the magnetic particles remain there while being washed away. In some embodiments, when the device is rotated at high speed, the magnetic particles are retained within the capture zone, and any liquid in the chamber can overflow into another reservoir without damaging the magnetic particles.

[0055] Referring to block 408, in some embodiments, the method includes (D) rotating (C) and then filling the chamber with fluid.

[0056] Referring to block 410, in some embodiments, the method includes (E) rotating the device relative to a magnet in order to move magnetic particles from the attachment into the chamber. The rotation of the device may be performed continuously or intermittently (e.g., in a series of angular positions).

[0057] Referring to block 412, in some embodiments, the method includes (F) aligning the ultrasonic probe with the chamber. In some embodiments, aligning (F) is achieved by rotating the device.

[0058] Referring to block 414, in some embodiments, the method includes (G) moving an ultrasonic probe or device so that the ultrasonic probe contacts a flexible capping layer.

[0059] Referring to block 416, in some embodiments, the method includes instigating an ultrasonic probe to deliver one or more pulses to facilitate mixing of (H) magnetic particles and a fluid.

[0060] Referring to block 418, in some embodiments, the method includes allowing the mixture in the chamber to be incubated for a certain period of time after (I) starting up (H).

[0061] In some embodiments, aligning (F), moving (G), and activating (H) are performed before positioning (A). In some embodiments, aligning (F), moving (G), and activating (H) are performed after rotating (E). In some embodiments, relative motion between the magnet and the chamber is achieved by moving the magnet, the device, or both. In some embodiments, the method includes repeating any one of the steps disclosed above.

[0062] Referring to Figure 7, a device 700 (e.g., a disk) according to an alternative and exemplary embodiment of the present disclosure is shown. In some embodiments, the device 700 (e.g., a disk) includes a plurality of units such as units 710-1, 710-2, 710-3, etc., arranged circumferentially. In some embodiments, the device 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 mechanisms / components / devices disclosed herein (e.g., a siphon valve structure 110). In some embodiments, each unit 710 includes one or more mechanisms / components / devices disclosed herein (e.g., a siphon valve structure 110). In some embodiments, each unit is identical to other units in the plurality of units. In some embodiments, at least one unit is different from other units in the plurality of units.

[0063] Exemplary Workflow Figures 6A–6J are schematic diagrams illustrating exemplary workflows according to several exemplary embodiments of this disclosure. Note that while specific specimens (e.g., whole blood) are used to illustrate the workflows, this disclosure is not limited to them. Other specimens, such as those disclosed herein, may also be used. Furthermore, the workflows may be automated.

[0064] Referring to Figure 6A, a device 600 (e.g., a disk) is shown according to several exemplary embodiments of the present disclosure. For clarity, only a portion of the device is shown. The device 600 is rotatable about an axis of rotation, such as a vertical rotation axis 601. In some embodiments, the device 600 can be rotated at a speed 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 embodiments, the device 600 can be rotated at a maximum speed of approximately 500 rpm, 600 rpm, 700 rpm, 800 rpm, 900 rpm, 1000 rpm, 1200 rpm, 1400 rpm, 1600 rpm, 1800 rpm, 2000 rpm, 2200 rpm, 2400 rpm, 2600 rpm, 2800 rpm, 2900 rpm, 3000 rpm, 3500 rpm, 4000 rpm, 4500 rpm, or 5000 rpm during one or more processes.

[0065] The device 600 includes one or more ports, one or more chambers, one or more lanes, and one or more flow paths. For example, in the illustrated embodiment, the 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 and overflow chamber 614, a reporter chamber 616, a first wash buffer port 617, a wash buffer chamber 618 (also called a wash buffer slow lane 618), a wash buffer fast lane 619, a delay chamber 620, a McDot Lyo chamber 622, a siphon flow path 626, a reaction (Rxn) chamber 624, a particle attachment 628, a waste liquid chamber 630, and a vent 646. In some embodiments, the Rxn chamber 624 includes or contains lyophilized reagent beads 640. In some embodiments, the lyophilized reagent beads 640 include magnetic particles and antibodies. Device 600 is shown with certain components (e.g., specific chambers, flow paths), but it should be noted that this is an example and not limiting. In some embodiments, device 600 may not include one or more of these specific components. In some embodiments, device 600 may include additional or alternative components, such as those disclosed herein.

[0066] Device 600 can be used to perform a variety of immunoassays. Representative immunoassays that can be performed with Device 600 include, but are not limited to, free thyroxine hormone (T4), thyroid-stimulating hormone (TSH), type b natriuretic peptide BNP such as N-terminal pro-BNP, C-reactive protein (CRP), vitamin D, prostate-specific antigen (PSA), ferritin, D-dimer, testosterone, and troponin, or combinations thereof in a sample.

[0067] Referring to Figure 6B, the sample and buffer introduction process according to some exemplary embodiments of the present disclosure is illustrated. In this process, a sample (e.g., whole blood) is introduced into the sample chamber 604 and a dilution buffer is introduced into the dilution buffer chamber 602. In some embodiments, the sample is a whole blood sample. In some embodiments, the buffer is a mixture of TBST dilution buffer, e.g., Tris-buffered saline (TBS) (buffer solution) and polysorbate 20 (polysorbate-type nonionic surfactant).

[0068] Referring to Figure 6C, the spin process according to several exemplary embodiments of the present disclosure is illustrated. In some embodiments, the device 600 is spun at high speed around a vertical rotation axis 601. In some embodiments, the sample (e.g., whole blood sample) is moved to the sample separation chamber 606. As the device 600 is spun, the whole blood sample is separated into plasma and cellular components. The dilution buffer is moved to the mixing chamber 610 and the mixing / metering chamber 612. Furthermore, the dilution buffer is metered in the mixing / metering chamber 612. If there is any excess dilution buffer, the excess dilution buffer is pneumatically and overflows into the overflow chamber 614.

[0069] Referring to Figure 6D, sample pretreatment processes according to several exemplary embodiments of the present disclosure are illustrated. In some embodiments, the plasma component of the sample can be flowed from the sample separation chamber 606 to the sample weighing chamber 608 by slowing the rotation of the device 600. As the rotation of the device 600 slows, the air pressure and the air trapped in the overflow chamber 614 expand, pushing the TBST dilution buffer from the mixing / weighing chamber 612 into the mixing chamber 610, thus moving the TBST dilution buffer from the mixing / weighing chamber 612 to the mixing chamber 610.

[0070] In some embodiments, with respect to timing, when the rotation of device 600 slows down, the TBST dilution buffer flows from the mixing / measuring chamber 612 to the mixing chamber 610 before the plasma flows from the sample separation chamber 606 to the sample weighing chamber 608. In this way, the plasma is prevented from flowing toward the mixing chamber 610, and the plasma can be weighed within the sample weighing chamber 608.

[0071] Referring to Figures 6E-1 and 6E-2, injection and mixing processes according to several exemplary embodiments of the present disclosure are illustrated. In some embodiments, plasma is measured from the sample metering chamber 608 to the mixing chamber 610 by increasing the rotational speed of device 600. The metered plasma is mixed with TBST dilution buffer by accelerating and decelerating the rotation of device 600. This causes the air pressure and trapped air in the overflow chamber 614 to expand and contract, causing the plasma / TBST dilution buffer mixture to reciprocate.

[0072] Referring to Figures 6F-1 and 6F-2, the reconstitution and pull-down processes of lyophilized beads according to several exemplary embodiments of the present disclosure are shown. In some embodiments, the rotational speed of device 600 is reduced. This causes the air pressure and the trapped gas in the overflow chamber 614 to expand, thereby pushing the plasma / dilution buffer mixture from the mixing / metering chamber 612 and the mixing chamber 610 through the siphon 625 into the reaction (Rxn) chamber 624.

[0073] In some embodiments, the magnetic particles and antibodies in the lyophilized reagent beads 640 (e.g., as shown in Figure 6A) are dissolved during this process.

[0074] In some embodiments, additionally or optionally, an ultrasonic probe (e.g., as shown in Figure 3C) is brought into contact with the Rxn chamber 624 to mix its contents. For example, in some embodiments, the ultrasonic probe is used to rapidly homogenize the reaction mixture.

[0075] Referring to Figures 6G-1 and 6G-2 together with Figures 6F-1 and 6F-2, a washing process (e.g., a first washing) according to several exemplary embodiments of the present disclosure is shown. In some embodiments, the magnetic particles 638 can be isolated within the particle attachment 628 by positioning a magnet 636 close to the particle attachment 628. In some embodiments, a washing buffer is added to the washing buffer high-speed lane 619 and the washing buffer chamber 618 (also called the buffer low-speed lane 618). When the device 600 is spun, the washing buffer in the washing buffer high-speed lane 619 moves to the Rxn chamber 624, combines with the diluted plasma mixture, and then moves to the waste chamber 630. The washing buffer in the washing buffer low-speed lane 618 is held in the delay structure 620 during this time and eventually flows into the Rxn chamber 624 and the waste chamber 630. In some embodiments, the magnetic particles 638 remain within the particle attachment 628 during this process.

[0076] Referring to Figures 6H-1 and 6H-2, the reconstitution and incubation processes of reporter lyophilized beads according to several exemplary embodiments of the present disclosure are shown. In some embodiments, a buffer is added to the reporter chamber 616. The device 600 is spun to force the buffer from the reporter chamber 616 into the reporter Lyo chamber 622, dissolve the reporter lyophilized beads 623, and then flow them into the Rxn chamber 624. In some embodiments, the device 600 stops spinning, and the magnetic particles 638 shown in Figures 6G-1 and 6G-2 are resuspended in the solution in the Rxn chamber 624, as shown in Figure 6H-2. In some embodiments, a static magnet 636 is used to move the magnetic particles 638 into the Rxn chamber 624, and / or an ultrasonic probe is used to achieve a uniform suspension.

[0077] Referring to Figures 6I-1 and 6I-2, particle pull-down and washing processes according to several exemplary embodiments of the present disclosure are shown. In some embodiments, after incubation, a magnet 636 is used to move the magnetic particles and bound reporter particles 638 into the particle attachment 628. In some embodiments, washing buffer is added to the washing buffer high-speed lane 619 and the washing buffer low-speed lane 618. In some embodiments, when the device 600 is spun, the washing buffer in the washing buffer high-speed lane moves to the Rxn chamber 624, combines with the reaction mixture, and then moves to the waste chamber 630. The washing buffer in the washing buffer low-speed lane is held in the delay structure 620 during this time and eventually flows into the Rxn chamber 624 and the waste chamber 630. In some embodiments, the magnetic particles 638 remain in the particle attachment 628 during this process.

[0078] Referring to Figure 6J, the resuspend particle and readout process according to several exemplary embodiments of the present disclosure is shown. In some embodiments, the buffer is added to the wash buffer chamber 618. The device 600 is spun to transfer the buffer from the wash buffer chamber 618 to the Rxn chamber 624. As illustrated in Figures 6I-1 and 6I-2, the magnetic particles bound to the reporter particle 638 are resuspended and mixed with the TBST buffer in the Rxn chamber 624, for example, using an ultrasonic probe. In some embodiments, the Rxn chamber 624 is then aligned under a readout sensor for result detection.

[0079] The devices and methods disclosed herein may 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 WO2022 / 029732, the contents of which are incorporated herein by reference in their entirety. The devices and methods disclosed herein may be operated or carried out by systems similar to those disclosed in U.S. Patent Application No. 17 / 371,746, the contents of which are incorporated herein by reference in their entirety.

[0080] Examples of subject technologies defined by clauses Various examples of the aspects of this disclosure are set forth in numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples and are not intended to limit the subject art.

[0081] Clause 1. A device comprising: a rotating shaft; a ventilation port; a siphon having a top positioned radially outward with respect to the rotating shaft than the ventilation port; a ballast chamber having a first outlet connected to the ventilation port; and a second outlet connected to the inlet of the siphon, wherein the first outlet of the ballast chamber is positioned radially inward with respect to the rotating shaft than the second outlet of the ballast chamber and radially outward from the top of the siphon, thereby dividing the ballast chamber into a non-ventilated ballast portion radially inward of the first outlet and a ventilated ballast portion radially outward of the first outlet.

[0082] Clause 2. The device according to Clause 1, wherein the second outlet of the ballast chamber is formed at or near the radially outermost position of the ballast chamber.

[0083] Clause 3. The device according to any of the preceding clauses, further comprising a first flow path connecting the first outlet of the ballast chamber to the ventilation port.

[0084] Clause 4. The device according to any of the preceding clauses, further comprising an upstream chamber connected to the ballast chamber.

[0085] Clause 5. The device according to Clause 4, wherein the ballast chamber is provided with an inlet for the non-ventilated ballast portion, and the upstream chamber is connected to the inlet for the non-ventilated ballast portion of the ballast chamber.

[0086] Clause 6. The device according to any one of Clauses 4 to 5, wherein the upstream chamber comprises an outlet connected to the ballast chamber, and the top and vent port of the siphon are radially inward from the outlet of the upstream chamber.

[0087] Clause 7. The device according to Clause 6, wherein the outlet of the upstream chamber is formed at the radially outermost position of the upstream chamber.

[0088] Clause 8. The device according to any one of Clauses 4 to 7, further comprising a U-shaped channel connecting the ballast chamber to the upstream chamber.

[0089] Clause 9. The device according to Clause 8, wherein the volume in the ballast chamber located inward from the first outlet is greater than the volume required to pass over the top of the siphon.

[0090] Clause 10. The device according to any of the preceding clauses, further comprising a downstream chamber connected to the outlet of the siphon.

[0091] Clause 11. The device according to Clause 10, wherein the downstream chamber is positioned radially outward from the second outlet.

[0092] Clause 12. The device according to any of the preceding clauses, wherein the vent port, the siphon, the ballast chamber, the first flow path, the upstream chamber, the U-shaped flow path, or any combination thereof is configured to allow initial filling of the fluid by rotating the device at a speed such that the ballast chamber and the siphon are filled with fluid to form a first meniscus inside the ballast chamber radially inward of the first outlet and a second meniscus inside the siphon radially outward of the top of the siphon.

[0093] Clause 13. The device according to Clause 12, wherein the vent port, the siphon, the ballast chamber, the first flow path, the upstream chamber, the U-shaped flow path, or any combination thereof is configured to allow discharge from the upstream chamber by reducing the velocity.

[0094] Clause 14. The device according to Clause 12, wherein the vent port, the siphon, the ballast chamber, the first flow path, the upstream chamber, the U-shaped flow path, or any combination thereof is configured to allow discharge from the upstream chamber by increasing the velocity.

[0095] Clause 15. The device according to any one of Clauses 13 to 14, wherein the vent port, the siphon, the ballast chamber, the first flow path, the upstream chamber, the U-shaped flow path, or any combination thereof is configured to allow complete discharge of the upstream chamber.

[0096] Clause 16. A device comprising: a rotating shaft; a chamber; an attachment comprising an inlet connected to the chamber and a capture zone radially outward from the inlet with respect to the rotating shaft; and a magnet; a magnetic particle movable between the chamber and the attachment by positioning the chamber relative to the magnet, rotation of the device, or any combination thereof.

[0097] Clause 17. The device according to Clause 16, wherein the chamber comprises a flexible capping layer that facilitates mixing of the magnetic particles with the fluid in the chamber in response to one or more ultrasonic pulses.

[0098] Clause 18. The device according to any one of Clauses 16 to 17, wherein the magnetic particles are magnetic nanoparticles.

[0099] Clause 19. A method comprising: (A) positioning the chamber of a device adjacent to a magnet such that magnetic particles contained within the chamber form a first arrangement; (B) rotating the device with respect to the magnet to move the magnetic particles into an attachment connected to the chamber, the attachment comprising an entrance and a capture zone radially outward from the entrance with respect to the rotation axis of the device; and (C) rotating the device at a rate that washes out unbound specimens or nonspecifically bound particles from the chamber, such that the magnetic particles remain within the capture zone.

[0100] Clause 20. The method of Clause 19, wherein the arrangement (A) is carried out by rotating the device.

[0101] Clause 21. The method according to any one of Clauses 19 to 20, wherein the magnet generates the strongest magnetic field in the central portion of the chamber.

[0102] Clause 22. The method described in any one of Clauses 19 to 21, wherein the rotation (B) is carried out continuously.

[0103] Clause 23. The method described in any one of Clauses 19 to 21, wherein the rotation (B) is performed intermittently.

[0104] The method according to any one of the clauses 19 to 22, further comprising (D) filling the chamber with fluid after the rotation (C), and (E) rotating the device with respect to the magnet to move the magnetic particles from the attachment into the chamber.

[0105] Clause 25. The method of Clause 24, wherein the rotation (E) is carried out continuously.

[0106] Clause 26. The method of Clause 24, wherein the rotation (E) is performed intermittently.

[0107] Clause 27. The method according to any one of Clauses 19 to 26, wherein the chamber comprises a flexible capping layer, and the method further comprises (F) aligning the chamber with an ultrasonic probe, (G) moving the ultrasonic probe or the device such that the ultrasonic probe is in contact with the flexible capping layer, and (H) activating the ultrasonic probe to deliver one or more pulses to facilitate mixing of the magnetic particles with the fluid.

[0108] Clause 28. The method of Clause 27, wherein the alignment (F) is achieved by rotating the device.

[0109] Clause 29. The method described in any one of Clauses 27 to 28, wherein the aligning (F), moving (G), and starting (H) are performed prior to the positioning (A).

[0110] Clause 30. The method according to any one of Clauses 27 to 28, wherein the aligning (F), moving (G), and starting (H) are performed after the rotating (E).

[0111] The method according to any one of the clauses 27 to 30, further comprising (i) allowing the mixture in the chamber to be incubated for a certain period of time after the initiation (h).

[0112] Clause 32. A system for operating the device or for carrying out the method described in any of the preceding clauses.

[0113] Citation of terms and references The terms used herein are for the sole purpose of describing specific embodiments and are not intended to limit the scope of the claims. As used in the description of these embodiments and in the appended claims, the singular forms "a," "an," and "the" are intended to also include the plural form unless the context otherwise explicitly indicates. Terms such as "left" or "right," "top" or "bottom," "underside" or "upper," "internal" or "external," "inside" or "outside" will be understood to be used to describe features of exemplary embodiments by referring to the location of features as shown in the figures. In this specification, terms such as "first," "second," etc., may be used to describe various elements, but it will be understood that these elements should not be limited by these terms. These terms are used merely to distinguish one element from another. For example, the first element may be referred to as the second element, and similarly, the second element may be referred to as the first element, without changing the meaning of the description, as long as "first element" and "second element" are renamed in a consistent manner.

[0114] Where used herein, the term “and / or” refers to and encompasses any possible combination of one or more of the related enumerated items. Furthermore, where used herein, the terms “include,” “includes,” “including,” “comprise,” “comprises,” and / or “comprising” express the presence of the described features, integers, steps, actions, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, actions, elements, components, and / or groups thereof.

[0115] The terms “approximately” or “about” are used herein to provide a literal justification for a number that is a neighbor or approximation of the number that follows, as well as the number itself. When determining whether a number is close to or approximately equal to a specifically stated number, an unstated but close or approximate number may be substantially equivalent to the specifically stated number in the given context. All numbers and ranges disclosed herein should be understood as approximations and approximation ranges, regardless of whether “approximately” is used in connection therewith. When used herein in conjunction with a number, the term “approximately” should be interpreted as referring to values ​​within ±0.01%, ±0.1%, ±0.5%, ±1%, ±2%, ±3%, ±5%, ±10%, or ±15% of that number. Furthermore, where a numerical range is disclosed in this specification, it will be understood that any numerical value that falls within that range is also specifically disclosed.

[0116] As used herein, the term "if" is optionally interpreted, depending on the context, as meaning "when," "upon," "in response to determining," "in response to detecting," or "in accordance with a determination that." Similarly, as used herein, the phrases "if it is determined" or "[a ​​stated condition or event] is detected" are optionally interpreted, depending on the context, as meaning "upon determining," "in response to determining," "upon detecting [the stated condition or event]," "in response to detecting [the stated condition or event]," or "in accordance with a determination that [a stated condition or event] is detected."

[0117] When a reference number is given the notation "i-th", that reference number refers to a general component, set, or embodiment. For example, "unit i" refers to the i-th unit of a group of units.

[0118] All references cited herein are incorporated herein by reference in any and all for any and all for any and all for any and all for the same degree as each individual publication or patent or patent application is specifically and individually indicated to be incorporated herein by reference in any and all for

Claims

1. It is a device, The axis of rotation and Ventilation port, A siphon having a top portion positioned radially outward from the ventilation port or any portion of the flow path connected to the ventilation port with respect to the rotation axis, The ballast chamber comprises a first outlet connected to the ventilation port and a second outlet connected to the inlet of the siphon, The device wherein the first outlet of the ballast chamber is positioned radially inward with respect to the axis of rotation from the second outlet of the ballast chamber and radially outward from the top of the siphon, thereby dividing the ballast chamber into a non-ventilated ballast portion radially inward from the first outlet and a ventilated ballast portion radially outward from the first outlet.

2. The device according to claim 1, wherein the second outlet of the ballast chamber is formed at or near the radially outermost position of the ballast chamber.

3. The device according to claim 1, further comprising a first flow path connecting the first outlet of the ballast chamber to the ventilation port.

4. The device according to claim 1, further comprising an upstream chamber connected to the ballast chamber.

5. The device according to claim 4, wherein the ballast chamber is provided with an inlet for the non-ventilated ballast portion, and the upstream chamber is connected to the inlet for the non-ventilated ballast portion of the ballast chamber.

6. The upstream chamber is equipped with an outlet connected to the ballast chamber, The device according to claim 4, wherein optionally, the top of the siphon and the vent port are radially inward from the outlet of the upstream chamber.

7. The device according to claim 6, wherein the outlet of the upstream chamber is formed at the radially outermost position of the upstream chamber.

8. The device according to claim 4, further comprising a U-shaped channel connecting the ballast chamber to the upstream chamber.

9. The device according to claim 8, wherein the volume of the ballast chamber located inside the first outlet is greater than the volume required to pass over the top of the siphon.

10. The device according to claim 1, further comprising a downstream chamber connected to the outlet of the siphon.

11. The device according to claim 10, wherein the downstream chamber is positioned radially outward from the second outlet.

12. It is a device, The axis of rotation and Chamber and, An attachment comprising an inlet connected to the chamber and a capture zone located radially outward from the inlet with respect to the axis of rotation, The device comprises a magnet, magnetic particles that are movable between the chamber and the attachment by positioning the chamber relative to the magnet, rotating the device, or any combination thereof.

13. The device according to claim 12, wherein the chamber comprises a flexible capping layer that facilitates mixing of the magnetic particles with the fluid in the chamber in response to one or more pulses.

14. The device according to claim 13, wherein the pulse is generated using an ultrasonic probe in contact with the capping layer.

15. The device according to claim 12, wherein the magnetic particles are magnetic nanoparticles.

16. It is a method, (A) Arranging the chamber of the device adjacent to the magnet such that the magnetic particles contained in the chamber form a first arrangement, (B) Rotating the device with respect to the magnet in order to move the magnetic particles into an attachment connected to the chamber, wherein the attachment comprises an entrance and a capture zone radially outward from the entrance with respect to the rotation axis of the device, (C) The method comprising rotating the device at a rate that washes away unbound specimens or nonspecifically bound particles from the chamber, wherein the magnetic particles remain in the capture zone along with the remaining liquid volume.

17. The method according to claim 16, wherein the arrangement (A) is carried out by rotating the device.

18. (D) After the rotation (C), the chamber is filled with fluid, (E) The method according to claim 16, further comprising rotating the device with respect to the magnet in order to move the magnetic particles from the attachment to the chamber.

19. The chamber is provided with a flexible capping layer, and the method is (F) Aligning the chamber with the ultrasonic probe, (G) Moving the ultrasonic probe or the device such that the ultrasonic probe comes into contact with the flexible capping layer, (H) The method according to claim 18, further comprising activating the ultrasonic probe to deliver one or more pulses to facilitate mixing of the magnetic particles and the fluid.

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

21. The method according to claim 20, further comprising (i) enabling the mixture in the chamber to be incubated for a certain period of time after the activation (H).

22. The chamber is provided with a flexible capping layer, and the method is (D) After the rotation (C), the chamber is filled with fluid, (E) Aligning the chamber with the ultrasonic probe, (F) Moving the ultrasonic probe or the device such that the ultrasonic probe comes into contact with the flexible capping layer, (G) The method according to claim 16, further comprising activating the ultrasonic probe to deliver one or more pulses to move the magnetic particles out of the capture zone and to promote mixing of the magnetic particles with the fluid.

23. The method according to claim 22, wherein the alignment (E) is achieved by rotating the device.

24. The method according to claim 22, further comprising (H) enabling the mixture in the chamber to be incubated for a certain period of time after the activation (G).

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