Microfluidic sample handling

Abstract

Structures, devices, and methods for treating fluids are provided. The valve includes a first passage having a first inlet connected to the upstream chamber. The first inlet of the first channel has a cross-section perpendicular to the flow direction that is the same as or smaller than the upstream chamber, and thus forms a hydrophobic junction with the upstream chamber at the first inlet. The valve also includes a compartment connected to a first outlet of the first passage. The compartment has a larger cross-section perpendicular to the flow direction than the first outlet of the first channel and thus forms a hydrophilic junction at the first outlet of the first channel.

Description

TECHNICAL FIELD

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 489,424, filed March 10, 2023, and U.S. Provisional Patent Application No. 63 / 489,681, filed March 10, 2023. The disclosure of each application is incorporated herein by reference in its entirety for all purposes. TECHNICAL FIELD

[0002] The present disclosure relates to devices and methods for handling fluids, and in particular to devices and methods for handling fluids in microfluidics. BACKGROUND

[0003] Currently, 70% of all medical decisions rely on laboratory-based diagnostics, but today the diagnostic process is out of sync with the way healthcare is delivered. Primary care systems require patients to travel to an external blood draw site to have blood drawn, which is sent to a lab via courier and processed overnight. This means that lab results arrive in the hands of healthcare professionals long after the patient has left. This friction in healthcare delivery and disease management results in huge waste in the healthcare system: a. Patients often delay taking a lab test or fail to comply with lab tests or subsequent healthcare recommendations b. Gaps in the diagnostic process result in missed tests, missed diagnoses, lack of intervention, and ultimately poor outcomes c. Healthcare professionals waste time tracking down lab orders and corresponding patient visit records. When intervention is needed, more time is wasted contacting the patient and pushing through subsequent steps in the patient’s healthcare pathway.

[0004] These problems are even more acute when providing healthcare to rural populations or patients belonging to groups facing adverse social determinants of health, where there are many challenges in ensuring that follow-up visits are successfully completed from the initial patient visit.

[0005] Several companies have developed point-of-care instruments to bridge this gap. However, these instruments are limited to a single type of test and do not fully meet the workflow needs of primary care providers for a single system that produces simple, comprehensive, and rapid test results. A product is currently being developed that meets these needs. It does so through a highly automated workflow that is achieved through the use of centrifugal microfluidic discs.

[0006] Centrifugal microfluidic technology is used in clinical chemistry, immunoassays, hematology, medicine, biomedical research, and other fields. These applications often require metering, transferring, mixing fluids, and / or other processes. Many of these applications also require detecting concentrations and reactions. However, in microfluidic technology, achieving effective control of metering, transferring, and mixing of fluids and accurate measurement of concentrations and reactions can be a challenge because, due to the small scale involved, the behavior of liquids can be significantly different from their bulk counterparts.

[0007] Therefore, there remains a need for improved devices and methods in centrifugal microfluidic technology to meet these and other needs in the art. SUMMARY

[0008] In a first aspect, the disclosure provides a simple and reliable valve that integrates both hydrophobic and hydrophilic principles into a single simple structure and eliminates the need for surface treatment. The valve includes a first channel and a compartment. The first channel has a first inlet and a first outlet. The first inlet is connected to an upstream chamber and has a cross-section perpendicular to the flow direction that is the same as or smaller than the upstream chamber, thereby forming a hydrophobic junction with the upstream chamber at the first inlet. The compartment is connected to the first outlet of the first channel. The compartment has a cross-section perpendicular to the flow direction that is larger than the first outlet of the first channel, thereby forming a hydrophilic junction at the first outlet of the first channel.

[0009] In some embodiments, the compartment is deeper, wider, or both than the first channel. In some embodiments, the compartment is cylindrical. In some such embodiments, the compartment has a circular, oval, oblong, or polygonal cross-section.

[0010] In some embodiments, the valve further includes a second channel having a second inlet and a second outlet. The second inlet is connected to the compartment and the second outlet is connected to a downstream chamber. In an embodiment, the second channel has a cross-section perpendicular to the flow direction that is the same as the first channel. In another embodiment, the second channel has a cross-section perpendicular to the flow direction that is different from the first channel. In some embodiments, the second channel is longer than the first channel.

[0011] In a second aspect, the disclosure provides a device that includes a valve disclosed herein and an upstream chamber. In some embodiments, a portion of the upstream chamber adjacent to the first inlet of the first channel of the valve is tapered to make a smooth transition between the upstream chamber and the first inlet of the first channel of the valve.

[0012] In some such embodiments, the tapering portion of the upstream chamber has a trapezoidal cross-section parallel to the flow direction. In some embodiments, the tapering portion of the upstream chamber is configured at least in part based on the fluid to be processed by the device. In some embodiments, the tapering portion of the upstream chamber has an angle of about -10 to -30 degrees, about -30 to -60 degrees, or about -60 to -80 degrees relative to the first channel.

[0013] In a third aspect, this disclosure provides an apparatus having a structure for trapping residual fluid. The apparatus rotates about an axis of rotation. The apparatus includes a channel for transferring fluid by rotating the apparatus about the axis of rotation. The channel includes an inlet, an outlet located radially outside the inlet relative to the axis of rotation, and a first portion between the inlet and the outlet. The apparatus also includes a structure connected to a first side of the first portion of the channel. The structure is configured to: (i) allow the transfer of the fluid when the apparatus rotates at a first speed; (ii) collect fluid residue when the apparatus rotates at a second speed greater than the first speed; and (iii) trap the collected fluid residue within the structure when the apparatus is subjected to acceleration, deceleration, or both.

[0014] In some embodiments, the structure includes a recess for containing the fluid residue and a chamber connecting the recess to a first side of the first portion of the channel. The chamber has a greater depth than the first portion of the channel and the recess, thereby acting as a valve between the first portion of the channel and the recess.

[0015] In some embodiments, at least a portion of the structure is located radially outward of the first portion of the channel, and the maximum permissible level of the fluid residue is defined by the innermost point of the junction formed by the chamber and the first side of the first portion of the channel. In some embodiments, a second side of the first portion of the channel is located radially inward of the maximum permissible level of the fluid residue. In some embodiments, the first portion of the channel is bent.

[0016] In a fourth aspect, this disclosure provides an apparatus for inertial mixing of fluids having two or more different components. The apparatus rotates about a rotation axis. The apparatus includes a mixing chamber having a curved side not coaxial with the rotation axis and is configured for inertial mixing of fluids having two or more different components.

[0017] In a fifth aspect, this disclosure provides a method for inertial mixing of fluids having two or more different components. The method includes (A) an apparatus comprising a rotation axis and a mixing chamber having a curved side not coaxial with the rotation axis, wherein the mixing chamber contains a fluid comprising two or more different components. In some embodiments, the volume of the fluid is at most 50%, at most 55%, at most 60%, at most 65%, or at most 70% of the volume of the mixing chamber.

[0018] The method further includes (B) accelerating the device to a first velocity in a direction toward the curved side of the mixing chamber. In some embodiments, the first velocity is based at least in part on the type of fluid, the amount of fluid, the shape of the mixing chamber, or any combination thereof.

[0019] The method further includes (C) abruptly decelerating the device, causing the fluid to move towards the curved side of the mixing chamber due to inertia. The curved side of the mixing chamber converts the movement of the fluid into a circular motion that generates vortices, thereby promoting the mixing of the two or more different components in the fluid. In some embodiments, the deceleration (C) is performed at a deceleration of at least 500 rpm / s, at least 1000 rpm / s, at least 1500 rpm / s, at least 2000 rpm / s, or at least 2500 rpm / s, at least 3000 rpm / s, at least 5000 rpm / s, 10000 rpm / s, at least 50000 rpm / s, or greater. In some embodiments, the deceleration (C) brings the device to a complete stop.

[0020] In some implementations, the method further includes (D) repeating the acceleration (B) and deceleration (C) once or multiple times.

[0021] In some embodiments, the mixing chamber includes a passage on a side opposite to the curved side and not coaxial with the axis of rotation. In some such embodiments, the method further includes: (E) slowly accelerating the device at a second speed in a direction toward the passage; and (F) suddenly decelerating the device such that the fluid moves toward the passage of the mixing chamber due to inertia. In some embodiments, the second speed is based at least in part on the type of fluid, the amount of fluid, the shape of the mixing chamber, or any combination thereof.

[0022] In a sixth aspect, this disclosure provides a method for guiding a fluid flow by inertia. The method includes: (A) obtaining a device having a rotation axis and a chamber having a passage not coaxial with the rotation axis, wherein the chamber contains fluid; (B) accelerating the device in a direction toward the passage toward the chamber; and (C) abruptly decelerating the device such that the fluid moves toward the passage of the chamber due to inertia.

[0023] In a seventh aspect, this disclosure provides a capillary channel capable of bubble-free pre-filling. The capillary channel includes an open end and a dead end, the dead end being positioned radially outward of the open end relative to an axis of rotation. The capillary channel also includes a first flow channel, a second flow channel, and a third flow channel. The first flow channel has an inlet at the open end for receiving fluid. The third flow channel has an outlet at the open end for discharging air. A second flow channel is formed between and connected to the first and third flow channels. The second flow channel has a different flow resistance than the first and third flow channels, thereby allowing the fluid to first flow from the open end through the first flow channel to the dead end, and then from the dead end through the second flow channel, the third flow channel, or both to the open end to facilitate bubble-free pre-filling.

[0024] In some embodiments, the first, second, and third flow channels together form a stepped cross-section perpendicular to the length direction of the capillary channel. In some embodiments, the first and third flow channels are deeper than the second flow channel. In some embodiments, the first and third flow channels are substantially identical to each other. In another embodiment, the first and third flow channels are different from each other. In some embodiments, at least two of the first, second, and third flow channels have the same width. In some embodiments, at least two of the first, second, and third flow channels have different widths.

[0025] In an eighth aspect, this disclosure provides an apparatus rotatable about a rotation axis. The apparatus includes a ventilation port and a capillary channel disclosed herein. The capillary is positioned radially outside the ventilation port, wherein the outlet of the third flow path of the capillary channel is connected to the ventilation port.

[0026] In a ninth aspect, this disclosure provides an apparatus having a clamping structure for guiding fluid flow. The apparatus includes a chamber and a channel connected to the chamber for delivering fluid into the chamber. The chamber and the channel together form a junction that minimizes or eliminates capillary flow as fluid flows from the outlet of the channel into the chamber. In some embodiments, the junction allows fluid to flow into the chamber from the outlet of the channel in the direction of centrifugal force.

[0027] In some embodiments, the channel includes a protruding portion forming at least a portion of the joint. In one embodiment, the protruding portion includes a U-shaped wall located on each side of the channel at the channel's outlet. In another embodiment, the protruding portion includes a V-shaped wall located on each side of the channel at the channel's outlet. In some embodiments, the wall of the chamber adjacent to the channel's outlet is radially inwardly curved relative to the channel's outlet to form at least a portion of the joint.

[0028] In a ninth aspect, this disclosure provides a method for measuring depth with self-calibration capability. The method includes (A) obtaining an apparatus comprising a structure filled with an absorbing dye. The structure includes a first portion having a first depth and a second portion having a second depth. The first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known. In some embodiments, obtaining (A) includes: obtaining the apparatus having the structure; and filling the structure with the absorbing dye.

[0029] The method further includes: (B) measuring a first optical density of the absorbing dye at the first portion of the structure and a second optical density of the absorbing dye at the second portion of the structure; and (C) calculating an optical density difference between the first optical density and the second optical density. The method further includes (D) calculating a ratio of the optical density difference to the nominal depth difference. The ratio represents the product of the extinction coefficient and concentration of the absorbing dye. Furthermore, the method includes (E) using the ratio to determine the first depth of the first portion of the structure, the second depth of the second portion of the structure, the depth of any additional structure of the device, or any combination thereof.

[0030] In a tenth aspect, this disclosure provides a self-calibrating apparatus for measuring depth. The apparatus includes one or more structures, each structure including a first portion having a first depth and a second portion having a second depth. The first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known, thereby allowing self-calibration of the depth of any structure of the apparatus independent of variations in its manufacture.

[0031] In some embodiments, one or more structures include a first structure and a second structure located at different locations in the device. In one embodiment, the nominal depth difference of the first structure is the same as that of the second structure. In another embodiment, the nominal depth difference of the first structure is different from that of the second structure.

[0032] In an eleventh aspect, this disclosure provides a method for measuring concentration unaffected by manufacturing variability. The method includes (A) an apparatus comprising a structure located in a passage of a mixture having a first component. The structure includes a first portion having a first depth and a second portion having a second depth. The first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known. In some embodiments, the first component is hemoglobin.

[0033] The method further includes (B) measuring a first optical density of the first component at the first portion of the structure and a second optical density of the first component at the second portion of the structure. In some embodiments, the absorbance measurement is performed using a spectrophotometer or a microfluidic device.

[0034] The method further includes: (C) calculating the optical density difference between the first optical density and the second optical density; and (D) determining the concentration of the first component in the mixture based at least in part on the optical density difference and the nominal depth difference. In some embodiments, the concentration of the first component in the mixture is determined by comparing the optical density difference with a calibration curve at an optical path corresponding to the nominal depth difference. In some embodiments, the extinction coefficient of the first component is known, and the concentration of the first component in the mixture is calculated by dividing the optical density difference by the nominal depth difference and the extinction coefficient of the first component.

[0035] In some embodiments, the method further includes (E) creating the calibration curve prior to the determination (D). In some embodiments, the creation (E) includes: (i) preparing a series of standard solutions having known concentrations of the first component; (ii) measuring the absorbance of each of the standard solutions at one or more specific wavelengths for the first component at one or more optical paths to obtain a plurality of absorbance values; and (iii) plotting the absorbance values ​​against the corresponding concentrations of the first component to create the calibration curve for each of the one or more optical paths.

[0036] In a twelfth aspect, this disclosure provides an apparatus for measuring concentration independently of manufacturing variations. The apparatus includes a structure located in a passage of a mixture having a first component. The structure includes a first portion having a first depth and a second portion having a second depth. The first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known, thereby allowing the measurement of the concentration of the first component independent of variations in the manufacture of the apparatus.

[0037] 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 and the following detailed description, which together serve to explain certain principles of the exemplary embodiments of this disclosure. Attached Figure Description

[0038] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate one or more exemplary embodiments of the present disclosure and, together with the detailed description, 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, locations, and shapes) will be determined in part by the particular intended application and environment of use. Furthermore, the components illustrated in the figures can be combined in any useful number and combination.

[0039] In the attached diagram: FIG. 1A This is a schematic diagram illustrating an apparatus including a valve according to some exemplary embodiments of the present disclosure, wherein the valve is in a hydrophobic scenario; FIG. 1B This illustrates an exemplary embodiment according to the present disclosure. FIG. 1A A schematic diagram of the device, in which the valve is in a hydrophilic environment; FIG. 1C This is an example along FIG. 1A A schematic diagram of the cross-section of the device, shown by the dashed line in the diagram; FIG. 1DThis is a schematic cross-sectional view illustrating an apparatus according to an alternative exemplary embodiment of the present disclosure; FIG. 1E This is a schematic diagram illustrating an existing steam trap; FIG. 1F This is a schematic diagram illustrating an existing hydrophilic valve; FIG. 2A These are images illustrating an apparatus having a structure for trapping residual fluid according to some exemplary embodiments of the present disclosure; FIG. 2B This is a schematic diagram illustrating a structure for retaining residual fluid according to some exemplary embodiments of the present disclosure; FIG. 2C It is along FIG. 2B A cross-sectional view taken from the vertical line in the image; FIG. 2D It is an image showing a device that does not have a structure for trapping residual fluid; FIG. 3 This is a flowchart illustrating a method for inertial mixing of fluids having two or more different components according to some exemplary embodiments of the present disclosure; FIG. 4A The image illustrates an apparatus for inertial mixing of fluids having two or more different components according to an exemplary embodiment of the present disclosure. FIG. 4B The image illustrates an apparatus for inertial mixing of fluids having two or more different components, according to an alternative exemplary embodiment of the present disclosure. FIG. 4C This is an image illustrating an apparatus for inertial mixing of fluids having two or more different components, according to another alternative exemplary embodiment of this disclosure; FIG. 4D This is an image illustrating an apparatus for inertial mixing of fluids having two or more different components, according to yet another alternative exemplary embodiment of the present disclosure; FIG. 5 This is a flowchart illustrating a method for guiding fluid flow by inertia according to some exemplary embodiments of the present disclosure; FIG. 6 These are images illustrating an apparatus for guiding fluid flow by inertia according to some exemplary embodiments of the present disclosure; FIG. 7A These are images illustrating an apparatus having capillary channels capable of bubble-free pre-filling according to some exemplary embodiments of the present disclosure; FIG. 7B These are examples of some exemplary embodiments according to this disclosure. FIG. 7A A cross-sectional view of the capillary channel; FIG. 8A These are images illustrating a device having a clamping structure for guiding fluid flow according to some exemplary embodiments of the present disclosure; FIG. 8B This illustrates an exemplary embodiment according to the present disclosure. FIG. 8A A schematic diagram of the clamping structure; FIG. 8C This illustrates alternative exemplary embodiments according to this disclosure. FIG. 8A A schematic diagram of the clamping structure; FIG. 8D and FIG. 8E It is an image showing a device without a clamping structure for guiding fluid flow; FIG. 9 This is a flowchart illustrating a method for measuring depth with self-calibration capability according to some exemplary embodiments of the present disclosure; FIG. 10A The image illustrates an apparatus with a structure for measuring depth that has self-calibration capability, according to some exemplary embodiments of the present disclosure; FIG. 10B These are examples of some exemplary embodiments according to this disclosure. FIG. 10A A cross-sectional view of the structure; FIG. 11 This is a flowchart illustrating a method for measuring concentration in an unaffected by manufacturing variability according to some exemplary embodiments of the present disclosure; FIG. 12A These are images illustrating an apparatus having a structure for measuring concentration unaffected by manufacturing variations, according to some exemplary embodiments of the present disclosure; FIG. 12B These are examples of some exemplary embodiments according to this disclosure. FIG. 12A A cross-sectional view of the structure; FIG. 13 This is a schematic diagram illustrating an apparatus (e.g., a disk) according to some exemplary embodiments of the present disclosure; FIG. 14 This is a schematic diagram illustrating an apparatus (e.g., a disk) according to some exemplary embodiments of the present disclosure; FIG. 15 This is a block diagram illustrating the workflow of some exemplary embodiments according to this disclosure; FIG. 16A-1 It is a schematic diagram and FIG. 16A-2 These are photographs illustrating a buffer loading process according to some exemplary embodiments of this disclosure; FIG. 16B-1 It is a schematic diagram and FIG. 16B-2 These are photographs illustrating a sample loading process according to some exemplary embodiments of this disclosure; FIG. 16C-1 It is a schematic diagram and FIG. 16C-2 These are photographs illustrating a buffer overflow process according to some exemplary embodiments of this disclosure; FIG. 16D-1 It is a schematic diagram and FIG. 16D-2 These are photographs illustrating a sample overflow process according to some exemplary embodiments of this disclosure; FIG. 16E-1 It is a schematic diagram and FIG. 16E-2 These are photographs illustrating a sample measurement process according to some exemplary embodiments of this disclosure; FIG. 16F-1 It is a schematic diagram and FIG. 16F-2 These are photographs illustrating a buffer metering process according to some exemplary embodiments of this disclosure; FIG. 16G-1 It is a schematic diagram and FIG. 16G-2 These are photographs illustrating a rotational acceleration process according to some exemplary embodiments of this disclosure; FIG. 16H-1 It is a schematic diagram and FIG. 16H-2 These are photographs illustrating a mixing process according to some exemplary embodiments of this disclosure; FIG. 16I-1 It is a schematic diagram and FIG. 16I-2 These are photographs illustrating a first measurement process according to some exemplary embodiments of this disclosure; FIG. 16J-1 It is a schematic diagram and FIG. 16J-2 These are photographs illustrating a second measurement process according to some exemplary embodiments of this disclosure; FIG. 16K-1 It is a schematic diagram and FIG. 16K-2 These are photographs illustrating a third measurement process according to some exemplary embodiments of this disclosure; FIG. 16L-1 It is a schematic diagram and FIG. 16L-2 These are photographs illustrating a sample separation process according to some exemplary embodiments of this disclosure; and FIG. 16M-1 It is a schematic diagram and FIG. 16M-2 and FIG. 16M-3 The photograph illustrates a self-calibration process according to some exemplary embodiments of this disclosure. Detailed Implementation

[0040] Simplified and reliable valve design Microfluidic systems typically require valves to regulate fluid flow, but existing solutions are limited by factors such as the need for multiple components, complex fabrication processes, or surface treatments. For example, known solutions often require multiple components and complex fabrication processes, increasing the cost and complexity of device manufacturing. Furthermore, known solutions often require surface treatments (such as coatings) to achieve the hydrophobicity or hydrophilicity required for proper valve performance. These treatments add additional steps to the manufacturing process and limit the range of materials that can be used. Moreover, known solutions are often limited in their applicability to certain materials or environmental conditions and may only work with hydrophobic or hydrophilic materials, or may be sensitive to changes in temperature or humidity. Additionally, known solutions often lack means to prevent sample drying (e.g., blood drying) and / or cell sedimentation, which can cause blockage of microfluidic channels.

[0041] Hydrophobic materials repel water and do not allow water to spread on their surface, while hydrophilic materials attract water and allow water to spread on their surface. This results in the following behaviors: FIG. 1E As illustrated, liquid 102 will stop at the inlet of the narrow hydrophobic area in the channel, and if the valve is hydrophilic, then... FIG. 1F As illustrated, the liquid stops at the widened part of the capillary channel.

[0042] Steam traps rely on the interaction between the liquid and the valve disc material to control the flow of liquid through microfluidic channels. They are typically made of hydrophobic materials (such as certain plastics) to prevent the liquid from wetting the valve surface. Steam traps usually include a constriction or hydrophobic plate area in the channel, which creates a pressure drop that prevents liquid from flowing through the valve. To open the valve, the liquid pressure must increase above a certain threshold to overcome the pressure drop and allow the liquid to flow through the valve. One advantage of steam traps is that they do not require surface treatments (such as hydrophobic coatings) to maintain their hydrophobicity. This makes them more cost-effective and easier to use than other types of valves, especially for mass production. Additionally, hydrophobic materials are relatively inert and chemically resistant, making them suitable for a wide range of applications, including those involving corrosive or aggressive liquids.

[0043] In the case of hydrophilic materials, the liquid spreads and wets the surface, increasing the total surface area in contact with air, thereby reducing pressure and causing the liquid to move upwards along the channel. Hydrophilic valves utilize the liquid meniscus pinning phenomenon to control the flow of liquid through microfluidic channels. When a liquid comes into contact with a solid surface, it forms a meniscus that remains at the point of maximum curvature, thus preventing further flow. By carefully designing the channel size and geometry, the burst pressure can be controlled, and when the pressure exceeds a certain threshold, the valve can be triggered to open or close. The burst pressure is determined by several factors, including channel size, surface tension, and the liquid contact angle. The smaller the channel size, the greater the surface tension required to maintain the liquid meniscus. Conversely, a larger channel will require a smaller surface tension to maintain the meniscus. The liquid contact angle is equally important because it determines the degree to which the liquid wets the channel surface, which in turn affects the strength of the liquid-solid interaction. Hydrophilic valves have many important applications in microfluidics and lab-on-a-chip devices, where they are used to precisely control the flow of liquids and manipulate small amounts of fluid.

[0044] The stability of steam traps and hydrophilic valves can be affected by changes in the hydrophobicity or hydrophilicity of the materials used to manufacture the valves, which may cause the valves to become less efficient or even fail completely.

[0045] This disclosure addresses these and / or other needs by providing a simplified valve that is more efficient and reliable in controlling the flow of fluids, particularly those containing blood. The simplified valve of this disclosure integrates both hydrophobic and hydrophilic principles into a single, simple structure and eliminates the need for surface treatments. This makes the fabrication of microfluidic devices easier and more cost-effective, and provides improved reliability and performance. In some embodiments, the simplified valve of this disclosure includes sections designed to prevent fluid drying and cell sedimentation, which helps ensure reliable valve performance even with more viscous materials (e.g., more viscous blood).

[0046] Now for reference FIG. 1A to FIG. 1C The diagram illustrates an apparatus 100 according to some embodiments of the present disclosure. The apparatus 100 includes an upstream chamber 110, a downstream chamber 120, and a valve 130 configured to connect the upstream and downstream chambers. The valve 130 typically includes a first channel 140 and a compartment 150. The first channel and the compartment are configured such that the first channel forms a hydrophobic junction with the upstream chamber, for example, acting as a hydrophobic valve, and the compartment forms a hydrophilic junction with the first channel, for example, acting as a hydrophilic valve.

[0047] For example, in some embodiments, the first channel 140 has a first inlet 141 and a first outlet 142. The first inlet 141 is connected to the upstream chamber 110 and has a cross-section perpendicular to the flow direction that is the same as or smaller than that of the upstream chamber. Thus, it forms a hydrophobic junction with the upstream chamber to stop fluid at the first inlet of the first channel (if the junction is hydrophobic). The compartment 150 is connected to the first outlet of the first channel and has a cross-section perpendicular to the flow direction that is larger than that of the first outlet of the first channel. Thus, it forms a hydrophilic junction to stop fluid at the first outlet of the first channel (if the junction is hydrophilic). In some embodiments, the compartment is deeper, wider, or both than the first channel. In some embodiments, the compartment is cylindrical. In some embodiments, the compartment has a circular, oval, oblong, or polygonal cross-section.

[0048] Because valve 130 integrates both hydrophobic and hydrophilic principles into a single structure, it offers greater stability and reliability, while also providing a wider range of applications. For example, it can regulate liquid flow even if one of its features is compromised. This contributes to improved overall valve reliability and stability, and expands its range of applications. Compared to conventional hydrophobic or hydrophilic valves, combining both hydrophobic and hydrophilic features in a single valve improves performance and allows for a wider range of applications. Furthermore, it allows for optimization of one or more dimensions (e.g., length, width, height) of the first channel and / or compartment without any surface patterning to ensure reliable valve operation under both types of conditions. For example, in some specific implementations, the width of the first channel may be approximately 100 μm to approximately 200 μm, approximately 200 μm to approximately 300 μm, approximately 300 μm to approximately 400 μm, or approximately 400 μm to approximately 500 μm. The depth of the first channel can be about 100 μm to about 200 μm, about 200 μm to about 300 μm, about 300 μm to about 400 μm, or about 400 μm to about 500 μm. The length of the first channel can be about 200 μm to about 400 μm, about 400 μm to about 600 μm, about 600 μm to about 800 μm, or about 800 μm to about 1000 μm. However, this disclosure is not limited thereto. For example, depending on the application, the first channel may be smaller, shorter, larger, or longer. The width or depth of the first channel can be at least 0.5 mm, at least 0.6 mm, at least 0.7 mm, at least 0.8 mm, at least 0.9 mm, or at least 1 mm. The length of the first channel can be at least 1 mm, at least 5 mm, at least 1 cm, at least 2 cm, at least 3 cm, at least 4 cm, or at least 5 cm.

[0049] Valve 130 may include additional, optional, or alternative features. For example, in some embodiments, valve 130 includes a second channel 160 configured to prevent the sample from drying out. In some embodiments, the second channel 160 connects the compartment to a downstream chamber; for example, the second channel has a second inlet 161 connected to the compartment and a second outlet 162 connected to the downstream chamber.

[0050] The addition of a second channel helps minimize sample (e.g., blood) evaporation, surface hydration, and / or moisture condensation in microfluidic systems. Sample evaporation, surface hydration, and / or moisture condensation can cause significant problems in microfluidic applications, including sample volume loss, channel blockage, surface contaminant formation, and sample quality degradation. For example, blood drying is a major problem in blood analysis applications. Drying can lead to red blood cell blockage, causing valve failure and potentially affecting analytical accuracy. A second channel can help reduce these effects by providing a longer, more restricted path for the sample, thereby reducing the sample's exposure to air and other environmental factors. This helps slow evaporation and surface hydration rates and prevents moisture condensation, thus helping to maintain sample integrity and quality. Careful control of sample exposure to the environment is crucial for the overall performance and reliability of the system.

[0051] The second channel may be configured identically to or differently from the first channel. For example, in some embodiments, the second channel has the same cross-section (e.g., width and depth) as the first channel, perpendicular to the flow direction. Alternatively, in some embodiments, the second channel has a different cross-section perpendicular to the flow direction than the first channel. In some typical embodiments, the second channel is longer than the first channel.

[0052] The optimization of the length, width, and / or depth of the second channel may depend on whether the channel is blocked during evaporation. In some embodiments, the aspect ratio of the length to width and the aspect ratio of the length to depth of the second channel are greater than 2, greater than 3, greater than 4, or greater than 5. For example, in some specific implementations, the length of the second channel is about 1 mm to 5 mm, and the width or depth is about 150 μm to about 400 μm. However, this disclosure is not limited thereto. For example, depending on the application, the length of the second channel may reach several centimeters or greater.

[0053] refer to FIG. 1DIn some embodiments, the junction between the upstream chamber 110 and the valve inlet (e.g., the first inlet 141 of the first channel) is configured to reduce clogging due to cell sedimentation. For example, in some such embodiments, the portion 112 of the upstream chamber 110 adjacent to the first inlet of the first channel of the valve is tapered to allow a smooth transition between the upstream chamber and the first inlet of the first channel of the valve. In some embodiments, the tapered portion of the upstream chamber has a trapezoidal cross-section parallel to the flow direction. In some embodiments, the tapered portion of the upstream chamber is configured at least in part based on the fluid 102 to be processed by the device. In some embodiments, the tapered portion of the upstream chamber has an angle of about -10 to -30 degrees, about -30 to -60 degrees, or about -60 to -80 degrees relative to the first channel. However, this disclosure is not limited thereto. Depending on the application (e.g., the fluid to be processed), the portion 112 of the upstream chamber 110 may have different shapes, sizes, and / or angles.

[0054] The design of the junction between the upstream chamber (e.g., the blood sample compartment) and the valve inlet plays a crucial role in preventing channel blockage due to cell sedimentation. For example, using a junction with... FIG. 1D The illustrated trapezoidal shape (not) FIG. 1C The illustrated rectangular shape helps reduce the likelihood of channel blockage by decreasing the sharpness of the transition between the upstream chamber and the first channel. The trapezoidal shape provides a smoother transition between the two sections and thus reduces the risk of cells being trapped or settling at the junction, potentially leading to blockage. This contributes to improved overall valve performance and reliability, maintains sample flow through the channel, and ensures the valve functions as intended even with more viscous blood materials.

[0055] The valve disclosed herein offers numerous advantages over existing solutions. For instance, regarding complexity, existing solutions typically require multiple components, complex fabrication processes, or surface treatments, increasing the complexity of microfluidic devices and making them more difficult to manufacture and maintain. The valve disclosed herein integrates both hydrophobic and hydrophilic principles into a single, simplified structure, thus reducing the number of required components and fabrication steps. Regarding reliability, existing solutions may be insufficiently reliable for some applications because they can become inefficient if surface or sample properties change, or if there is a delay between the time the sample arrives at the valve and the time it passes through the valve. The valve disclosed herein combines simplified components in a single structure, thus allowing the valve to operate more reliably under a wider range of material, sample, and environmental conditions. Regarding cost, surface treatments and complex fabrication processes can be expensive, making the production of existing microfluidic devices prohibitively costly for some applications. The valve disclosed herein eliminates the need for surface treatments, thus reducing the cost of manufacturing microfluidic devices. Furthermore, the passive nature of the valve, driven by the centrifugal force generated by the rotational speed of the device (e.g., cartridge), eliminates the need for external actuation and reduces the overall cost of manufacturing the fluid device. Regarding evaporation and cell sedimentation, existing solutions may not be effective in preventing sample drying (e.g., blood drying) or cell sedimentation, which can lead to valve malfunction. The valves or devices disclosed herein include features for preventing evaporation and cell sedimentation (e.g., a tapered portion of the second channel and upstream chamber), thereby ensuring reliable valve performance even with more viscous blood materials. Furthermore, the valves and devices disclosed herein allow for flexibility in material selection. The ability to use a wide range of materials, including both hydrophobic and hydrophilic materials, in cartridge fabrication opens up new possibilities for the design and manufacture of fluid devices. The valves and devices disclosed herein can be adapted to different environmental conditions (such as temperature and humidity) and are suitable for a wider range of applications.

[0056] Overall, this disclosure provides a more efficient solution for controlling fluid flow in microfluidic devices by simplifying device design, improving reliability, reducing costs, and preventing evaporation and cell sedimentation. The combination of these design features enables the valves and devices of this disclosure to represent a significant advancement in the field of microfluidics and fluid devices, thereby offering potential benefits for a wide range of applications, including but not limited to biomedical and clinical applications.

[0057] Structure for trapping residual fluid In many applications, residual fluid (e.g., blood) 204 may temporarily accumulate at, for example, the bottom of a U-shaped channel, such as... FIG. 2DAs illustrated. However, residual fluid is not completely captured and, due to its high viscosity and / or other factors, it can be drawn into downstream chambers (e.g., metering chambers) in subsequent processes. Furthermore, temporarily accumulated fluid can clog channels to vents, creating negative pressure buildup that leads to uncontrolled fluid movement. A common solution is to add a long, deep U-shaped structure. However, there is insufficient space on the disc to accommodate such a structure, and a significantly larger fluid (e.g., blood) volume would be required. It is also possible that for very viscous samples, the dragging force cannot pull the blood without damaging it. This could lead to channel blockage and negative pressure buildup. This disclosure addresses these and / or other needs by providing a structure that not only traps residual liquid but also allows for controlled fluid flow.

[0058] refer to FIG. 2A to FIG. 2C The diagram illustrates an apparatus 200 according to some embodiments of the present disclosure. The apparatus 200 is rotatable about a rotation axis 202. The apparatus includes a channel 210 for transferring fluid by rotating the apparatus about the rotation axis. The channel 210 includes an inlet 211 and an outlet 212, the outlet being positioned radially outward of the inlet relative to the rotation axis. The channel 210 also includes a first portion 220 between the inlet and the outlet. The first portion has a first side 221 (e.g., one side of the channel at the first portion) and a second side 222 (e.g., the other side of the channel at the first portion). In some embodiments, the first portion of the channel may be bent. In some embodiments, the first side 221 may be positioned generally radially outward of its corresponding second side 222. In some embodiments, the first side 221 has a generally concave shape and / or the second side 222 has a convex shape relative to the interior of the first portion of the channel.

[0059] The device 200 also includes a structure 230 connected to a first side 221 of the first portion 220 of the channel. The structure 230 is configured to: (i) allow fluid transfer when the device rotates at a first speed; (ii) collect fluid residue (e.g., residual fluid) when the device rotates at a second speed greater than the first speed; and (iii) retain the collected fluid residue within the structure when the device is subjected to acceleration, deceleration, or both.

[0060] For example, in some embodiments, structure 230 includes a recess 240 for receiving fluid residue and a chamber 250 for connecting the recess to a first side of the first portion of the channel. The chamber 250 has a greater depth than the first portion of the channel and the recess, thus acting as a valve between the first portion of the channel and the recess. In some embodiments, the recess may be shallow, narrow, and / or relatively long so as to retain residual fluid within the recess even when the disc is subjected to strong acceleration and deceleration. For example, in some embodiments, the depth of the channel or recess may be up to 1 mm, up to 1.5 mm, or up to 2 mm, and the depth of the chamber may be at least 0.1 mm, at least 0.2 mm, at least 0.3 mm, at least 0.4 mm, or at least 0.5 mm deeper than the channel or recess. However, this disclosure is not limited thereto. The channel, chamber, and recess may have other shapes or sizes and may be positioned differently.

[0061] In some embodiments, at least a portion of the structure is located radially outward of the first portion of the channel. For example, in some embodiments, a groove 240 or a portion of such a groove is located radially outward of the first portion of the channel. In some embodiments, the radially innermost point on the junction formed by the chamber and the first side of the first portion of the channel defines the maximum permissible level of fluid residue (e.g., FIG. 2B (dashed line in the diagram). In some embodiments, the structure and / or operation are designed to ensure that the meniscus of residual fluid does not exceed the maximum permissible level. This allows air trapped in the recesses and / or chambers to have an outlet path.

[0062] In some embodiments, the second side 222 of the first portion of the channel is positioned radially inward of the maximum permissible level of fluid residue. For example, in some embodiments, the bend at the second side of the first portion is positioned radially inward of the maximum permissible level. This prevents potential blockage of the channel and allows fluid to be transferred when needed or desired.

[0063] During centrifugation, most of the fluid (e.g., blood) is carried downstream. However, some residue adheres to the channel surface. This residue is pushed across the maximum permissible level and collected at the bottom of the first section 220 of the channel by centrifugal force. As rotation accelerates, the centrifugal force acting on the remaining blood increases and eventually breaks through an obstruction (e.g., a valve formed by chamber 250 and the channel and / or recess) after reaching a threshold. The residue enters recess 240, and in some cases, depending on the rotational speed, the amount of residue, the structural configuration, and / or other factors, the residue will reach the very bottom of the recess. Thereafter, even when the device is subjected to acceleration, deceleration, or both, the residue will remain in the recess.

[0064] Inertial-based mixing chamber and method Mixing blood with buffer solutions in centrifugal microfluidics can present numerous technical challenges. For example, blood cells may be damaged or destroyed under high centrifugal forces, leading to hemolysis (red blood cell rupture) and the release of hemoglobin into the buffer solution. This can interfere with downstream analysis and affect the accuracy of results. Blood can also clot upon contact with certain materials or surfaces, particularly in microfluidic systems with high surface-to-volume ratios. This can cause blockages in channels or result in incomplete mixing of blood and buffer solutions. Furthermore, achieving complete and homogeneous mixing of blood and buffer solutions in centrifugal microfluidics can be challenging due to the small volumes and rapid rotational speeds involved. Incomplete mixing can lead to inaccurate or unreliable results.

[0065] Existing techniques for blood and buffer solutions include those disclosed in the following: “Batch-mode mixing on centrifugal microfluidic platforms,” Lab Chip, 5, 560-565 (2005); “Reciprocating flow-based centrifugal microfluidics mixer disclosed in Review of Scientific Instruments,” 80, 075102 (2009); and “Decanting and mixing of supernatant human blood plasma on centrifugal microfluidic platform,” Microsyst Technol 22, 861–869 (2016), the contents of which are incorporated herein by reference in their entirety for all purposes. However, these prior art techniques do not provide a satisfactory solution. This disclosure addresses these and other needs in the art by providing a chamber with curvature and using inertial motion to generate eddies to facilitate mixing.

[0066] refer to FIG. 3 A flowchart illustrating an exemplary method 300 for mixing fluids according to some embodiments of the present disclosure is shown. 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.

[0067] Referring to reference block 302, in some embodiments, method 300 includes (A) an obtaining device comprising a rotation axis and a mixing chamber having a curved side not coaxial with the rotation axis. The mixing chamber may be configured in any suitable shape and / or size and disposed at any suitable location on the device (e.g., a tray or cassette), provided that the curved side not coaxial with the rotation axis is present. The device may be used for any suitable application, including but not limited to mixing blood with buffer solutions.

[0068] For example, as a non-restrictive example, FIG. 4A An example is shown, a device 400-1 rotatable about a rotation axis 402-1 and including a chamber 410-1. The chamber 410-1 has a curved side 420-1 that is not coaxial with the rotation axis 402-1. As another non-limiting example, FIG. 4B An example is shown, a device 400-2 rotatable about a rotation axis 402-2 and including a chamber 410-2. The chamber 410-2 has a curved side 420-2 that is not coaxial with the rotation axis 402-2. As a further non-limiting example, FIG. 4C An example is shown, a device 400-3 rotatable about a rotation axis 402-3 and including a chamber 410-3. The chamber 410-3 has a curved side 420-3 that is not coaxial with the rotation axis 402-3. As a further, non-limiting example, FIG. 4D An example is shown, which is rotatable about a rotation axis 402-4 and includes a chamber 410-4. The chamber 410-4 has a curved side 420-4 that is not coaxial with the rotation axis 402-4.

[0069] The mixing chamber contains a fluid 404 comprising two or more different components. In some embodiments, the volume of the fluid is up to 50%, 55%, 60%, 65%, or 70% of the mixing chamber. However, this disclosure is not limited thereto. For example, in some embodiments, the volume of the fluid may exceed 70% of the mixing chamber. In some embodiments, the volume of the fluid may be at least 200 μL, at least 400 μL, at least 600 μL, at least 800 μL, or at least 1000 μL. In some embodiments, the volume of the fluid may be up to 200 μL, at most 150 μL, at most 100 μL, at most 90 μL, at most 80 μL, at most 70 μL, or at most 60 μL, at most 50 μL.

[0070] In some embodiments, the mixing chamber has inflection points or bends, such as inflection points / partitions 430-1, 430-2, 430-3, and 430-4, at which the curvature of the mixing chamber changes sign. In some embodiments, the inflection points / partitions are configured to prevent fluid flow to the inlet of the mixing chamber. In some embodiments, the circularity of the curved side of the mixing chamber is about 1 mm to about 10 mm, about 10 mm to about 20 mm, about 20 mm to about 30 mm, or greater.

[0071] Referring to block 304, in some embodiments, method 300 includes (B) accelerating the device to a first speed in a direction toward a curved side of the mixing chamber. The first speed may be based at least in part on the type of fluid, the amount of fluid in the mixing chamber, the shape of the mixing chamber, or any combination thereof. For example, in some particular implementations, the first speed may be about 300 rpm to about 500 rpm, about 500 rpm to 700 rpm, or about 700 rpm to about 1000 rpm. However, this disclosure is not limited thereto. For example, in some particular implementations, the first speed may be less than 300 rpm or more than 1000 rpm.

[0072] Referring to block 306, in some embodiments, method 300 includes (C) abruptly decelerating the device, causing the fluid to move towards a curved side of the mixing chamber due to inertia. As the fluid moves towards the curved side, the curved side of the mixing chamber converts the fluid's movement into a circular motion that generates vortices, thereby promoting the mixing of two or more different components in the fluid. In some embodiments, deceleration (C) brings the device to a complete stop. In some embodiments, deceleration (C) is performed at a deceleration of at least 500 rpm / s, at least 1000 rpm / s, at least 1500 rpm / s, at least 2000 rpm / s, or at least 2500 rpm / s, at least 3000 rpm / s, at least 5000 rpm / s, 10000 rpm / s, at least 50000 rpm / s, or greater. However, this disclosure is not limited thereto. For example, in some embodiments, deceleration (C) may be performed at a deceleration of less than 500 rpm / s.

[0073] Referring to block 308, in some embodiments, method 300 includes (D) repeating acceleration (B) and deceleration (C) one or more times. The method may repeat acceleration (B) and deceleration (C) any suitable number of times to produce adequate mixing. In some embodiments, the method may repeat acceleration (B) and deceleration (C) at least 2 times, at least 5 times, at least 10 times, at least 15 times, at least 20 times, at least 30 times, at least 40 times, or at least 50 times.

[0074] The method disclosed herein uses the curvature and inertial motion of a mixing chamber to generate eddies. This eddy motion generates shear forces, which can induce mixing of the fluid. This method is based on the principle that components or particles with different densities or viscosities in a fluid will respond differently to the same inertial force, resulting in relative motion between them and ultimately leading to mixing. The apparatus and method disclosed herein can reduce hemolysis and coagulation and improve mixing efficiency. It is simple in design and does not require the design / addition of new features or the use of different disk materials / surface coatings.

[0075] Inertial-based devices and methods for guiding fluids Many factors play a role in the movement or guidance of fluids in microfluidics. In microfluidic channels, capillary forces can far exceed centrifugal forces, leading to non-uniform flow patterns or flow stagnation. This can result in incomplete delivery, uneven sample distribution, and channel blockage. At high rotational speeds, fluid viscosity also affects flow behavior, leading to the formation of secondary flows and eddies, which can interfere with the desired flow pattern. Furthermore, certain types of components (such as detergents dissolved in buffer solutions) can alter surface tension or other parameters and therefore readily form bubbles. This can be incompatible with some centrifugal microfluidic systems and limit the types of examinations that can be performed using this technique.

[0076] To address these challenges, various techniques have been developed, such as optimizing channel design and surface coatings to control capillary forces and selecting appropriate fluids with suitable viscosity and surface tension. Furthermore, advanced and expensive microfluidic systems with active feedback and control mechanisms can be used to modulate flow patterns and ensure accurate results. Examples of such techniques or research include those disclosed in the following: “Frequency-dependent transversal flow control incentrifugal microfluidics,” Lab Chip, 2005, 5, 146-150; “The Effect of Moment of Inertia on the Liquids in Centrifugal Microfluidics,” Micromachines 2016, 7(12), 215; and “Demonstration of an efficient, compact and precise pumping method by centrifugal inertia for lab on disk platforms,” 2019 J. Micromech. Microeng. 29 075001, the contents of which are incorporated herein by reference in their entirety for all purposes. They require complex systems to move or guide fluids.

[0077] This disclosure addresses these and other needs in the art by developing a technique for guiding liquid flow in centrifugal microfluidics using the inertial force of the liquid during sudden deceleration and when the disk rotation comes to a stop. This technique involves a chamber and adjacent chambers connected by a wide channel to transfer liquid from one chamber to the other. As the disk's rotational speed experiences a rapid decrease, the liquid responds by continuing to move in a direction tangential to the disk's rotational speed vector. By carefully sizing the wide channel and taking into account factors such as air displacement and surface tension, the liquid can be guided to the target chamber without requiring an external power source or introducing additional complexity to the system.

[0078] refer to FIG. 5 A flowchart illustrating an exemplary method 500 for guiding fluid according to some embodiments of the present disclosure is shown. 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.

[0079] Referring to block 502, in some embodiments, method 500 includes (A) a receiving device having a rotation axis and a chamber having a passage not coaxial with the rotation axis, wherein the chamber contains fluid. For example, as a non-limiting example, FIG. 6 An example of a device 600 is shown, which is rotatable about a rotation axis 602 and includes a chamber 610. The chamber 610 includes a passage 620, for example, a channel connecting the chamber 610 to a downstream chamber. The chamber 610 contains fluid 604. In some embodiments, the chamber 610 includes a barrier 630 through which fluid must pass to enter the downstream chamber.

[0080] Referring to blocks 504 and 506, in some embodiments, method 500 includes: (B) accelerating the device in a direction toward the passage to the chamber; and (C) abruptly decelerating the device, causing fluid to move toward the passage to the chamber due to inertia. In some embodiments, acceleration (B) may result in a speed of at least about 200 rpm, at least about 400 rpm, at least about 600 rpm, at least about 800 rpm, or at least about 1000 rpm. In some embodiments, deceleration (C) is performed at a deceleration of at least 500 rpm / s, at least 1000 rpm / s, at least 1500 rpm / s, at least 2000 rpm / s, or at least 2500 rpm / s, at least 3000 rpm / s, at least 5000 rpm / s, 10000 rpm / s, at least 50000 rpm / s, or greater. In some embodiments, deceleration (C) brings the device to a complete stop. FIG. 6 This shows that a considerable volume of fluid was transferred to the downstream chamber.

[0081] Although FIG. 6 The chamber 610 is illustrated as a mixing chamber, but it should be noted that this is by way of example and not a limitation. Method 500 and the techniques can be applied to any other type of chamber. Furthermore, the shape, size, and position of chamber 610 and passage 620 can be easily modified to suit other applications. In some embodiments, the passage is configured to be wide enough to allow for easy fluid movement.

[0082] In an embodiment where chamber 610 is a mixing chamber, method 500 can be used to guide the fluid after mixing. Fluid mixing can be performed using method 300 or any other mixing technique (e.g., using magnetic particles). For example, refer back to the reference. FIG. 3 and FIG. 4CIn some embodiments, the mixing chamber 410-3 includes a passage 440 (e.g., a channel) opposite the curved side 420-3 of the mixing chamber. The passage 440 connects the mixing chamber 410-3 to a downstream chamber. In some embodiments, the mixing chamber 410-3 also includes a barrier 450 through which fluid must pass to enter the downstream chamber. In some such embodiments, method 300 may include: (E) slowly accelerating the device at a second velocity in a direction toward the passage; and (F) abruptly decelerating the device, causing the fluid to move toward the passage of the mixing chamber due to inertia.

[0083] Using inertia to guide flow has potential applications in a variety of microfluidic processes, such as sample preparation and analysis, drug delivery, and microscale synthesis. It eliminates the need for special surface coatings to control capillary forces, advanced and expensive microfluidic systems with active feedback and control mechanisms to modulate flow patterns and ensure accurate results, and the need to select appropriate fluids with suitable viscosity and surface tension. Parameters such as chamber curvature, barrier height, passage length, width, and / or depth can be optimized to ensure reliable and reproducible results.

[0084] Channels capable of bubble-free pre-filling In microfluidics, it is difficult to remove all air bubbles from a capillary before it is filled with a sample. The presence of air bubbles can lead to errors in sedimentation analysis because it can alter the sedimentation rate of particles or interfere with the optical detection of the sedimentation process. One approach to achieving bubble-free prefilling is to remove air from the capillary using a vacuum or pressure system before filling it with a sample. However, this technique can be challenging to implement, especially for small-diameter capillaries or samples with low sedimentation rates. Another approach is to use surfactants or wetting agents to help displace air and wet the inner surface of the capillary. However, the choice of surfactant and its concentration can affect sedimentation rates, the morphology and integrity of delicate biological objects such as blood cells, and thus introduce additional sources of error. The use of a stepped channel has been proposed in “Single-step centrifugal hematocrit determination on a 10-$ processing device,” Biomed Microdevices (2007) 9:795–799, the contents of which are incorporated herein by reference in their entirety for all purposes. However, this stepped channel uses a hydrophilic surface treatment and relies on the capillary force required for pre-filling the channel. Overall, achieving bubble-free pre-filling of dead-end sedimentation capillaries requires careful attention to the selection of materials, methods, equipment, and sample preparation, as well as optimization of experimental conditions to ensure accurate and reproducible sedimentation analysis.

[0085] This disclosure addresses these and other needs in the art by providing a capillary channel in which pre-filling with liquid is based on the differentiation of flow resistance transmitted along different flow paths of the channel. Thus, the capillary channel of this disclosure can be made of any untreated material (including hydrophilic and hydrophobic materials) while still achieving bubble-free pre-filling.

[0086] refer to FIG. 7A and FIG. 7B The diagram illustrates an apparatus 700 according to some embodiments of the present disclosure. The apparatus 700 is rotatable about a rotation axis 702. The apparatus 700 includes a ventilation port 710 and a capillary channel 720 positioned radially outward of the ventilation port relative to the rotation axis 702.

[0087] The capillary channel 720 is configured with a stepped cross-section to facilitate bubble-free prefilling. It is designed to deliver fluid (e.g., blood) from the inlet into the blind-end capillary using differential fluid resistance driven by centrifugation. The unique depth profile of the capillary reliably prevents air trapping during the filling process.

[0088] The capillary channel 720 includes an open end 721 and a dead end 722, the dead end being positioned radially outward of the open end relative to the axis of rotation. The capillary channel may be oriented along a radius or at an angle to that radius. The angle may vary. In some embodiments, the angle may be in the range of 0-60 degrees. The capillary channel 720 also includes a first flow channel 730, a second flow channel 740, and a third flow channel 750. The first flow channel has an inlet at the open end for receiving fluid. The third flow channel has an outlet at the open end for discharging air. For example, in some embodiments, the outlet of the third flow channel of the capillary channel is connected to a vent port. The second flow channel is formed between and connected to the first and third flow channels. The first, second, and third flow channels are configured such that the second flow channel has a different flow resistance than the first and third flow channels, thereby allowing fluid to flow first from the open end 721 through the first flow channel 730 to the dead end 722, and then from the dead end 722 through the second flow channel 740, the third flow channel 750, or both to the open end 721 to facilitate bubble-free pre-filling.

[0089] In some implementations, the first, second, and third flow channels together form a stepped cross-section perpendicular to the length of the capillary channel, such as... FIG. 7BAs illustrated. In some embodiments, the first and third channels are deeper than the second channel; for example, a shallower second channel separates the deeper first and third channels. The adjoining extensions act as barriers, thereby creating two levels of fluid separation at adjacent edges. Fluid exposure to a lower resistance level promotes the filling of the dead-end channel, while air is removed through the higher resistance level as the fluid progresses downstream. When the fluid reaches the dead end of the capillary, it penetrates into the adjacent level to fill the capillary in the opposite direction without trapping air bubbles.

[0090] The third flow channel has a passage to the vent and is added for added reliability to broaden its application, especially when the fluid (e.g., blood) crosses the edge separating the first and second flow channels before reaching the dead end. This occurs if there are defects in the wall or the resistance difference is insufficient to achieve significant flow separation. This process ensures that the capillary is free of air bubbles. The number of flow channels does not have to be three. For example, there can be two or more than three, with the last flow channel having a passage to the vent.

[0091] The first and third flow channels may be configured to be substantially the same as each other (e.g., having the same width and depth) or different from each other (e.g., having different widths and / or different depths). In some embodiments, at least two of the first, second, and third flow channels have the same width. In some embodiments, at least two of the first, second, and third flow channels have different widths. In some specific implementations, the depths of the first and third flow channels may be about 500 µm to 1000 µm, about 1000 µm to 1500 µm, or about 1500 µm to 2000 µm. The second flow channel may be shallower than the first and / or third flow channels by about 200 µm to about 500 µm, about 300 µm to about 700 µm, or about 600 µm to 1000 µm. The radial length of the capillary channel may be at least 5 mm, at least 10 mm, at least 15 mm, at least 20 mm, at least 25 mm, or at least 30 mm. The width of each flow channel can be selected such that the flow resistance varies between shallow and deep channels. In some embodiments, the widths of the first, second, and / or third flow channels can range from about 100 µm to about 500 µm, about 300 µm to about 700 µm, or about 500 µm to 1000 µm. However, this disclosure is not limited thereto. Depending on the application, the channels including the first, second, and third flow channels can have any other suitable shape and size.

[0092] The capillary channel disclosed herein does not require a vacuum or pressure system to expel air from the capillary before it is filled with a sample, nor does it require a surfactant or wetting agent to help displace air and wet the inner surface of the capillary. It is simple and can be used in a variety of applications.

[0093] Clamping structure for guiding fluid Surface tension is a key factor in microfluidics, where the behavior of a liquid can differ significantly from its bulk counterpart due to the small scale involved. The interaction between the liquid and the channel walls can lead to a variety of phenomena, including capillary flow, where the liquid flows along the shape of the channel edge rather than in the direction of the applied force. In some cases, this can be undesirable and needs to be eliminated. For example, in microfluidics, surface tension can influence the direction of liquid flow after exiting the channel expansion, creating a meniscus or curved surface at the liquid-air interface. The shape and strength of the meniscus depend on the properties of the fluid, such as its surface tension, as well as the shape and surface properties of the channel. If the liquid has a high surface tension and the channel extension has edges with corners that promote wetting, the liquid will tend to diffuse and flow along the edges rather than in the direction of centrifugal force. This is known as capillary flow.

[0094] Surface interaction problems can arise when fluid leaves a small microfluidic channel and enters a larger chamber. The surface properties of the larger chamber at the junction can affect flow behavior, thus directing the fluid in an uncontrolled direction. For example, if the surface has inhomogeneous physical and chemical properties, the liquid may not flow out of the joint in the direction of centrifugal force, but rather along the angle of the joint, which can affect the operation of the system.

[0095] These technical problems can be mitigated by using surface treatments or adding surfactants. However, they add more cost to manufacturing, may potentially cause cell damage, and are complex. This disclosure addresses these and / or other problems in the art by providing an extension such that centrifugal force will act in the opposite direction to the capillary force vector, and thus compensate for that capillary force vector.

[0096] refer to FIG. 8A to FIG. 8C The diagram illustrates an apparatus 800 according to some embodiments of the present disclosure. The apparatus 800 is rotatable about a rotation axis 802. The apparatus 800 includes a chamber 810 and a channel 820 connected to the chamber for conveying fluid 804 into the chamber. The chamber and the channel together form a junction 830 that minimizes or eliminates capillary flow as fluid flows out of the channel (e.g., the channel's outlet) into the chamber. In some embodiments, this junction allows fluid to flow into the chamber from the channel's outlet in the direction of centrifugal force.

[0097] In some embodiments, the channel includes a protrusion 840 forming at least a portion of the junction. The protrusion 840 is configured such that fluid is held at the protrusion for a period of time until the centrifugal force exceeds the surface tension holding the fluid. During this holding time, there is no leftward or rightward movement of the fluid, while for FIG. 8D and FIG. 8E The straight edge shown illustrates this situation, where the flat wall allows fluid (e.g., blood) to flow unpredictably. Once the centrifugal force overcomes the surface tension, the fluid-surface interaction is broken, and the fluid will move in the direction of the centrifugal force. In this way, the direction of fluid flow can be predicted.

[0098] The protruding portion can be configured with any suitable shape and size. As a non-limiting example, FIG. 8B An example is illustrated by a protruding portion comprising a U-shaped wall 841 located on each side of the passage at the exit of the passage. As another non-limiting example, FIG. 8C An example is illustrated by a V-shaped wall 842 located on each side of the channel at the channel outlet. In some embodiments, the wall 811 of the chamber 810 adjacent to the channel outlet is radially inwardly bent relative to the channel outlet to form at least a portion of the junction. Fluid can be forced to move in a desired direction by applying a centrifugal force exceeding the surface tension. This is achieved by clamping the fluid at the channel extension, thereby creating a balancing torque between the forces, and then releasing the fluid when the centrifugal force becomes dominant.

[0099] In some specific implementations, the width of the channel may be about 100 μm to about 200 μm, about 200 μm to about 300 μm, about 300 μm to about 400 μm, or about 400 μm to about 500 μm, and / or the depth may be about 100 μm to about 200 μm, about 200 μm to about 300 μm, about 300 μm to about 400 μm, or about 400 μm to about 500 μm. In some embodiments, the radius of curvature of the U-shaped wall may be about 100 μm to about 200 μm, about 200 μm to about 300 μm, about 300 μm to about 400 μm, or about 400 μm to about 500 μm. However, this disclosure is not limited thereto. Depending on the application, the channel and protrusions may be configured in various shapes and sizes.

[0100] The clamping structure disclosed herein avoids the use of surface treatments, which would add to manufacturing costs and potentially cause cell damage. The clamping structure also avoids the need to add surfactants, which would be complex and potentially cause cell damage.

[0101] Apparatus and methods for measuring depth with self-calibration capability Variations in the depth of molded consumables can occur due to various reasons. Some of these are inconsistent molding conditions, where the depth can be affected by improper control of temperature, pressure, cooling rate, humidity, etc. To address these variability in the depth of molded consumables, appropriate measurement techniques must be used. Examples of techniques include profilometers, depth gauges, laser scanners, optical interferometry, and ultrasonic sensors. However, measuring the depth of each consumable during its assembly is a laborious and time-consuming process. Furthermore, the depth of a consumable may change over time with its use.

[0102] Uneven depths in some consumable compartments can cause unstable operation. For example, if the depth of the molded metering chamber in a microfluidic consumable varies, this can lead to a mismatch in the volume of fluid dispensed, potentially resulting in erroneous test results. Microfluidic consumables are used to accurately measure and dispose of small amounts of fluid in applications such as medical diagnostics, drug discovery, and gene analysis. Inaccurate metering due to variations in the depth of the molded metering chamber can lead to erroneous measurements, resulting in false positive or false negative results, which can have serious consequences in critical applications. Therefore, it is important to accurately measure the depth of the molded compartment in microfluidic consumables to ensure correct and reliable test results.

[0103] This disclosure addresses these and / or other problems in the art by implementing a self-calibration feature that can be used to measure production deviations in the depth of a device (e.g., molded consumables) directly at the user's site and / or as part of an analytical method. The measurement is both rapid (e.g., within a few seconds) and requires no human intervention.

[0104] refer to FIG. 9 A flowchart illustrating an exemplary method 900 for measuring depth unaffected by manufacturing variability, according to some embodiments of the present disclosure, is shown. 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.

[0105] Referring to block 902, in some embodiments, method 900 includes (A) a obtaining apparatus comprising a structure filled with an absorbent dye, wherein the structure includes a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known. For example, as a non-limiting example, FIG. 10A and FIG. 10BAn apparatus 1000 including structure 1010 is illustrated. Structure 1010 includes a first portion 1011 and a second portion 1012. The first portion 1011 has a first depth L1 and the second portion 1012 has a second depth L2. The first depth and the second depth are different from each other. These depths are not necessarily equal to their nominal values ​​because they are affected by manufacturing variations. However, the difference between these depths can correspond to the nominal depth difference because, in many cases, manufacturing variability has a similar effect on variation. In other words, although the first depth and the second depth may not be their nominal values, the nominal depth difference (ΔL) between the first depth and the second depth is known. In some embodiments, once the apparatus is obtained, absorbent dye is filled into the structure.

[0106] Referring to block 904, in some embodiments, method 900 includes (B) measuring a first optical density (OD1) of the absorber dye at a first portion of the structure and a second optical density (OD2) of the absorber dye at a second portion of the structure. In some embodiments, the first and second optical densities are measured using a spectrophotometer or a microfluidic device for measuring absorbance.

[0107] Reference box 906, in some embodiments, method 900 includes (C) calculating the optical density difference (ΔOD) between a first optical density and a second optical density.

[0108] Referring to box 908, in some embodiments, method 900 includes (D) calculating the ratio of the optical density difference to the nominal depth difference, where the ratio represents the product of the extinction coefficient of the absorbing dye and its concentration. For example, according to the Beer-Lambert law: Where e is the extinction coefficient of the absorbing dye, c is its concentration, and L1 and L2 are the depths of the first and second depths. It is not necessary to know the dye concentration and extinction coefficient.

[0109] In some implementations, this ratio is calculated as follows: Referring to block 910, in some embodiments, method 900 includes (E) using the ratio to determine a first depth of a first portion of the structure, a second depth of a second portion of the structure, the depth of any additional structures of the device, or any combination thereof. For example, in some embodiments, the obtained ratio (ec) is then substituted back into equation (1) to calculate the first depth L1 and / or substituted back into equation (2) to calculate the second depth L2.

[0110] Although FIG. 10A An example of a device having a structure 1010 is shown and FIG. 10BAn example of a structure 1010 with two different depths is illustrated, but it should be noted that the device may have more than one, two, three, four, five, or ten structures, and each structure may have more than two, three, four, or five different portions with different depths. These structures can be positioned at any suitable location on the device to allow for multiple measurements, thereby ensuring consistency of depth. These structures may be configured identically or differently from each other. They may also have different hierarchical pairs for calibrating deep and shallow channels, and may be two or more channels connected in series, or independent channels.

[0111] For example, in some embodiments, device 1000 includes one or more structures. Each of the one or more structures includes a first portion having a first depth and a second portion having a second depth. For each of the one or more structures, the first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known. This allows for self-calibration of the depth of any structure of the device (e.g., one or more structures or other structures) independent of variations in the manufacture of the device. In some embodiments, the one or more structures include a first structure and a second structure located at different locations within the device. In some such embodiments, the nominal depth difference of the first structure is the same as that of the second structure. Alternatively, in some embodiments, the nominal depth difference of the first structure is different from that of the second structure.

[0112] Apparatus and method for measuring concentration unaffected by manufacturing variations Measuring hemoglobin concentration is a crucial test for diagnosing anemia, monitoring blood loss, and assessing overall health. The use of microfluidic technology makes it possible to perform this test with small sample volumes and short time intervals. However, microfluidic consumables can exhibit manufacturing variability, which can affect the accuracy of test results. Various factors can cause manufacturing variability in the depth of molded consumables. Some of these are inconsistent molding conditions, where the depth of molded consumables can be affected by improper control of temperature, pressure, cooling rate, humidity, and / or other factors.

[0113] One way to address this issue is to calibrate the microfluidic device before use. Calibration involves determining the device's sensitivity and accuracy by measuring the hemoglobin concentration in a standard solution. This information can then be used to adjust the test results obtained from the device. However, this calibration relies on the consistency of consumable manufacturing. For example, if the concentration determination is based on hemoglobin optical density measurements, the optical pathway is a critical parameter. In this regard, the depth of the microfluidic optical compartment must be accurately determined.

[0114] This disclosure addresses these and / or other problems in the art by providing an apparatus and method for determining hemoglobin concentration by measuring the optical density of hemoglobin without requiring absolute depth determination. This approach is similar to methods used to measure manufacturing variability.

[0115] refer to FIG. 11 A flowchart illustrating an exemplary method 1100 for measuring concentration unaffected by manufacturing variability, according to some embodiments of the present disclosure, is shown. 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.

[0116] Referring to block 1102, in some embodiments, method 1100 includes (A) an apparatus comprising a structure located in a passage of a mixture having a first component, wherein the structure includes a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known. For example, as a non-limiting example, FIG. 12A and FIG. 12B An apparatus 1200 is illustrated, comprising a structure 1210 located in a passage 1220 having a mixture of first components (e.g., a mixture containing hemoglobin). Structure 1210 includes a first portion 1211 and a second portion 1212. The first portion 1211 has a first depth L1 and the second portion 1212 has a second depth L2. The first depth and the second depth are different from each other. These depths are not necessarily equal to their nominal values ​​because they are affected by manufacturing variations. However, the difference between these depths can correspond to a nominal depth difference because, in many cases, manufacturing variability has a similar effect on deviations. In other words, although the first depth and the second depth may not be their nominal values, the nominal depth difference (ΔL) between the first depth and the second depth is known.

[0117] Referring to reference block 1104, in some embodiments, method 1100 includes (B) measuring a first optical density (OD1) of a first component at a first portion of the structure and a second optical density (OD2) of the first component at a second portion of the structure. In some embodiments, the first and second optical densities are measured using a spectrophotometer or a microfluidic device for measuring absorbance.

[0118] Reference box 1106, in some embodiments, method 1100 includes (C) calculating the optical density difference (ΔOD) between a first optical density and a second optical density.

[0119] Referring to block 1108, in some embodiments, method 1100 includes (D) determining the concentration of a first component in the mixture based at least in part on the difference in optical density and the difference in nominal depth. For example, according to equations (1) and (2), ΔOD is a function of ΔL, as follows: Thus, the optical density difference (ΔOD) obtained from the calculation (C) can be compared with a calibration curve constructed for the same optical path as ΔL. A high-accuracy depth quartz cuvette can be used to create the calibration curve. Therefore, the output signal can be used to determine the concentration of the first component in the mixture (e.g., hemoglobin concentration). It is not necessary to know the extinction coefficient of the first component (e.g., hemoglobin) because the calibration curve is used.

[0120] In some implementations, if the extinction coefficient of the first component is known (e.g., determined for the wavelength used in the device's optical system), a calibration curve is not required. The concentration of the first component can be calculated using equation (4), for example, by dividing the optical density difference by the nominal depth difference and the extinction coefficient of the first component, since ΔOD, ΔL, and e are known.

[0121] Referring to blocks 1110 to 1116, in some embodiments, method 1100 includes (E) creating a calibration curve prior to determination (D). In some embodiments, creating (E) includes: (i) preparing a series of standard solutions having known concentrations of a first component; (ii) measuring the absorbance of each of the standard solutions at one or more specific wavelengths for the first component at one or more optical paths to obtain a plurality of absorbance values; and (iii) plotting the absorbance values ​​against the corresponding concentrations of the first component to create a calibration curve for each of the one or more optical paths.

[0122] For example, in some embodiments where the first component is hemoglobin, the method includes preparing a series of standard solutions having known concentrations of hemoglobin, using a spectrophotometer or microfluidic device to measure the absorbance of each of the standard solutions at a specific wavelength for hemoglobin, and plotting the absorbance values ​​against the corresponding hemoglobin concentration to create a calibration curve. In some embodiments, the method further includes measuring the absorbance of an unknown sample at the same wavelength used to measure the standard solutions, and / or using the calibration curve to determine the hemoglobin concentration of the unknown sample based on its absorbance value.

[0123] Similar to device 1000, device 1200 may have more than one structure 1210. Similarly, similar to structure 1010, structure 1210 may have more than two distinct parts. Furthermore, the device may have both structure 1010 and structure 1210 for performing both method 1000 and method 1200.

[0124] The apparatus and method of the present invention reduce the dependence of absorbance and thus concentration measurements on depth, and thus improve measurement accuracy.

[0125] refer to FIG. 13 The diagram illustrates an apparatus 1300 (e.g., a disk) according to some exemplary embodiments of the present disclosure. The apparatus 1300 is rotatable about a rotation axis (such as a vertical rotation axis 1303). In some implementations, the apparatus 1300 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, the device 1300 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 during one or more processes.

[0126] In some embodiments, device 1300 (e.g., a disk) includes a plurality of units arranged circumferentially, such as units 1310-1, 1310-2, and 1310-3. In some embodiments, device 1300 includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 units. In some embodiments, unit 1310 includes one or more features / components / devices disclosed herein (e.g., device / structure 100, device / structure 200, device / structure 400, device / structure 600, device / structure 700, device / structure 800, device / structure 1000, and / or device / structure 1200). In some embodiments, each unit 1310 includes one or more features / components / devices disclosed herein. In some embodiments, at least one unit is identical to another unit among a plurality of units. In some embodiments, at least one unit is different from other units among a plurality of units.

[0127] refer to FIG. 14 The diagram illustrates an apparatus 1400 (e.g., a disk) according to some exemplary embodiments of the present disclosure. The apparatus 1400 is rotatable about a rotation axis (such as a vertical rotation axis 1403). In some implementations, the apparatus 1400 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, the device 1400 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 during one or more processes.

[0128] In some embodiments, device 1400 (e.g., a disk) includes a plurality of units arranged circumferentially, such as units 1410-1, 1410-2, and 1410-3. In some embodiments, device 1400 includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 units. In some embodiments, unit 1410 includes one or more features / components / devices disclosed herein (e.g., device / structure 100, device / structure 200, device / structure 400, device / structure 600, device / structure 700, device / structure 800, device / structure 1000, and / or device / structure 1200). In some embodiments, each unit 1410 includes one or more features / components / devices disclosed herein. In some embodiments, at least one unit is identical to another unit among a plurality of units. In some embodiments, at least one unit is different from other units among a plurality of units.

[0129] Exemplary Workflow refer to FIG. 15 This document illustrates an exemplary workflow 1500 according to some exemplary embodiments of the present disclosure. Workflow 1500 can be performed on any suitable apparatus disclosed herein (e.g., apparatus 1300 or apparatus 1400). Workflow 1500 can also be automated. Furthermore, 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 processes exemplified in the present disclosure and workflow 1500 may, but need not, be performed in all of them or in the order they are presented.

[0130] Workflow 1500 can be configured to perform one or more assays, including but not limited to white blood cell (WBC) assays, red blood cell (RBC) assays, and / or hemoglobin (HgB) assays. In some embodiments, workflow 1500 can be configured to perform multiple assays, such as any two or all of the WBC, RBC, and hemoglobin assays. In some embodiments, workflow 1500 can be configured to perform one or more additional or optional processes, such as a self-calibration process.

[0131] In some embodiments, workflow 1500 includes process 1502 of loading a buffer solution (e.g., water) into a device (e.g., device 1400). Loading the buffer solution can be performed while the device is stationary or rotating at a low speed. In embodiments where multiple assays are to be performed, buffer solution can be loaded for all assays to be performed. As a non-limiting example, FIG. 16A-1 (Illustrative diagram) and FIG. 16A-2 (Photo) illustrates loading the buffer solution into device 1400.

[0132] In some embodiments, workflow 1500 includes a process 1504 of loading a sample (e.g., blood) into the device. Sample loading can be performed while the device is stationary or rotating at a low speed. Alternatively, sample loading can be performed before, simultaneously with, or after buffer loading. In embodiments where multiple assays are to be performed, buffer can be loaded for all assays to be performed. As a non-limiting example, FIG. 16B-1 (Illustrative diagram) and FIG. 16B-2 (Photo) illustrates loading a sample (e.g., blood) into device 1400. In some embodiments, the sample is loaded into the device and passes through a stepped retention channel (e.g., device / structure 200 disclosed herein) for all measurements.

[0133] In some embodiments, workflow 1500 includes a process 1506 of overflowing the buffer solution. During this process, the device (e.g., device 1400) is rotating and, in some cases, rotating at a predefined speed profile. In embodiments where multiple assays are to be performed, the overflow of the buffer solution may be performed simultaneously for all assays (e.g., measurements occur approximately simultaneously for all assays). As a non-limiting example, FIG. 16C-1 (Illustrative diagram) and FIG. 16C-2 (Photo) illustrates the overflow of buffer solution according to the design of device 1400.

[0134] In some embodiments, workflow 1500 includes a process 1508 of overflowing a sample (e.g., blood). During this process, the device (e.g., device 1400) is rotating and, in some cases, rotating at a predefined speed profile. In some embodiments, the sample is allowed to flow into or overflow into a hematocrit column, such as a bubble-free dead-end stepped channel (e.g., device 700 disclosed herein). In embodiments where multiple assays are to be performed, the overflow of the sample may be performed simultaneously for all assays (e.g., the measurements occur approximately simultaneously for all assays). As a non-limiting example, FIG. 16D-1 (Illustrative diagram) and FIG. 16D-2 (Photo) illustrates the sample overflow according to the design of device 1400.

[0135] In some embodiments, workflow 1500 includes a process 1510 of metering a sample (e.g., blood). During this process, the device (e.g., device 1400) is rotating and, in some cases, rotating at a predefined speed profile. In some embodiments, a valve (e.g., device / structure 100) is ruptured during this process. The sample is guided via a clamping channel (e.g., device / structure 800) to a mixing chamber (e.g., device / structure 400 or device / structure 600). In embodiments where multiple assays are to be performed, the metering of the sample may be performed simultaneously for all assays (e.g., metering occurs approximately simultaneously for all assays). As a non-limiting example, FIG. 16E-1 (Illustrative diagram) and FIG. 16E-2 (Photo) illustrates the measurement of a sample according to the design of device 1400.

[0136] In some embodiments, workflow 1500 includes a process 1512 for metering the buffer solution. During this process, the device (e.g., device 1400) is rotating and, in some cases, rotating at a predefined speed profile. In some embodiments, a valve (e.g., device / structure 100) is ruptured during this process. The buffer solution is guided via a clamping channel (e.g., device / structure 800) to a mixing chamber (e.g., device / structure 400 or device / structure 600). In embodiments where multiple assays are to be performed, the metering of the buffer solution may be performed simultaneously for all assays (e.g., metering occurs approximately simultaneously for all assays). In some embodiments, one or more sample chambers are also flash-evaporized during this process. As a non-limiting example, FIG. 16F-1 (Illustrative diagram) and FIG. 16F-2 (Photo) illustrates the metering of buffer solution according to the design of device 1400.

[0137] In some embodiments, workflow 1500 includes a process 1514 of retaining residual sample and / or allowing sample (e.g., blood) to overflow. During this process, rotation is accelerated (e.g., the rotational speed of the device is increased). In some embodiments, residual sample (if any) is retained. In some embodiments, excess sample (if any) is allowed to overflow into a hematocrit column. As a non-limiting example, FIG. 16G-1 (Illustrative diagram) and FIG. 16G-2 (Photo) illustrates how the device 1400 is designed to retain residual samples and / or allow samples to overflow.

[0138] In some embodiments, workflow 1500 includes a process 1516 of mixing a metered sample with a metered buffer solution. In some embodiments, mixing is achieved by alternately accelerating and decelerating the rotation of the device (e.g., by alternately increasing and decreasing the rotational speed of the device). Increasing / decreasing the rotational speed of the device (e.g., device 1400) can be repeated as needed, programmed, or continuously repeated until the solution is fully / thoroughly mixed. In some embodiments, increasing / decreasing the rotational speed of the device can be repeated about 10, about 20, about 30, about 40, about 50, or about 60 times. In embodiments where multiple assays are to be performed, the volumes of solutions for different assays may differ. However, the devices disclosed herein (e.g., device 1400) are configured such that the mixing efficiency is similar for all assays. This allows for simultaneous mixing of all assays (e.g., approximately simultaneous and / or approximately the same number of cycles for all assays).

[0139] In some embodiments, the principle of inertial motion is used in combination, for example, by increasing the rotational speed of the device to a threshold speed and then abruptly stopping the rotation (e.g., reducing the rotational speed to a low level or zero), as disclosed herein with respect to device / structure 400 and device / structure 600, thereby pushing the liquid to one side. This motion is entirely in one direction. This not only mixes the buffer solution with the sample but also dissolves the corresponding lyophilized reagents (e.g., lyophilized beads) in the chamber. As a non-limiting example, FIG. 16H-1 (Illustrative diagram) and FIG. 16H-2 (Photo) illustrates the mixing of a metered sample and a metered buffer solution according to the design of the device 1400.

[0140] In some embodiments, the mixing process dissolves lyophilized beads in a mixing chamber configured for WBC assay. The dissolved lyophilized beads cause RBC lysis and / or stain platelets as desired for fluorescence imaging. In some embodiments, the sample or solution becomes translucent. In some embodiments, WBCs are also labeled for fluorescence imaging. In some embodiments, the mixing process dissolves lyophilized beads in a mixing chamber configured for RBC assay. In some embodiments, the dissolved lyophilized beads stain platelets as desired for fluorescence imaging. In some embodiments, the mixing process dissolves lyophilized beads in a mixing chamber configured for HgB assay. In some embodiments, the dissolved lyophilized beads cause all cells to lyse to obtain a homogeneous, translucent mixture for use, for example, in hemoglobin absorbance measurements by imaging and / or other methods.

[0141] In some embodiments, workflow 1500 includes a process 1518 of delivering a mixture (e.g., a solution following a mixing process) to one or more detection channels (e.g., device / structure 1200) for measurement. In some embodiments, the mixture is delivered to its respective imaging channel by accelerating the rotation of the device in the opposite direction (e.g., in the direction opposite to the direction used for mixing) to a threshold speed and then abruptly stopping to push the mixture in the direction of rotation. In some embodiments, the device is then rotated at a low speed to allow the mixture to fill (e.g., completely fill) one or more detection channels or chambers. As a non-limiting example, FIG. 16I-1 (Illustrative diagram) and FIG. 16I-2 (Photo) illustrates the delivery of a mixture to one or more detection channels according to the design of device 1400.

[0142] In some embodiments, workflow 1500 includes a process 1520 for measuring the optical density (OD) of HgB. In some embodiments, the measurement of the optical density (OD) of HgB is performed using methods disclosed herein or similar methods. In some embodiments, the detection channel is a stepped optical channel (e.g., device / structure 1200). As a non-limiting example, FIG. 16I-1 (Illustrative diagram) and FIG. 16I-2 (Photo) illustrates the OD of HgB measured according to the design of device 1400.

[0143] Workflow 1500 may include one or more additional, optional, or alternative processes. For example, in some embodiments, workflow 1500 includes a process that allows for a WBC assay (e.g., for measuring the number of white blood cells in a blood sample). In some implementations, workflow 1500 includes additional or optional processes that allow cell sedimentation within one or more imaging channels configured for WBC assays, such as... FIG. 16J-1 (Illustrative diagram) and FIG. 16J-2 As illustrated in the photograph. After cells settle in the imaging channels, images are taken of each of one or more imaging channels and / or analyzed to perform WBC determination (e.g., WBC counting).

[0144] In some implementations, workflow 1500 includes procedures that allow RBC assays (e.g., for measuring the number of red blood cells in a blood sample). For example, in some implementations, workflow 1500 includes additional or optional procedures that allow cell sedimentation within one or more imaging channels configured for RBC assays, such as... FIG. 16K-1 (Illustrative diagram) and FIG. 16K-2 As illustrated in the photograph. After cells settle in the imaging channels, images are captured and / or analyzed in each of one or more imaging channels for RBC determination.

[0145] In some implementations, workflow 1500 includes a process that allows for hematocrit measurements (e.g., measuring the hematocrit level or the proportion of red blood cells in a blood sample). For example, in some implementations, workflow 1500 includes an additional or optional process for separating plasma from the blood sample. After all other assays have been performed (e.g., imaging the detection channels for all other assays), plasma can be separated from the blood sample (e.g., a blood sample from sample overflow) by rotating the device at a high speed, such as... FIG. 16L-1 (Illustrative diagram) and FIG. 16L-2 As illustrated in the photo.

[0146] In some implementations, workflow 1500 includes a process that allows for self-calibration. Self-calibration can be performed according to the method 900 and / or apparatus / structure 1000 disclosed herein. As a non-limiting example, FIG. 16M-1 (Illustrative diagram) FIG. 16M-2 (Photo) and FIG. 16M-3 (Photo) illustrates self-calibration according to the design of device 1400, which includes one or more devices / structures 1000 or structures similar to device / structure 1000.

[0147] 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 WO 2018 / 119437, WO 2018 / 140719, WO 2022 / 029731, and WO 2022 / 029732, the contents of each of which are incorporated herein by reference in their entirety. The apparatus and methods disclosed herein can be operated or performed by a system similar to the system disclosed in U.S. Patent Application No. 17 / 371,746, the contents of which are incorporated herein by reference in their entirety.

[0148] Description of the subject technology of the clause For convenience, various examples of aspects of this disclosure are described as numbered clauses (1, 2, 3, etc.). These are provided as examples and do not limit the subject matter.

[0149] Clause 1. A valve comprising: a first channel having a first inlet and a first outlet, wherein the first inlet is connected to an upstream chamber and has a cross-section perpendicular to the flow direction that is the same as or smaller than that of the upstream chamber, thereby forming a hydrophobic junction with the upstream chamber at the first inlet; and a compartment connected to the first outlet of the first channel, wherein the compartment has a cross-section perpendicular to the flow direction that is larger than that of the first outlet of the first channel, thereby forming a hydrophilic junction at the first outlet of the first channel.

[0150] Clause 2. The valve as described in Clause 1, the valve further comprising: a second passage having a second inlet and a second outlet, wherein the second inlet is connected to the compartment and the second outlet is connected to a downstream chamber.

[0151] Clause 3. The valve as described in Clause 2, wherein the second channel has the same cross-section as the first channel, perpendicular to the flow direction.

[0152] Clause 4. The valve as described in Clause 2, wherein the second channel has a cross-section that is different from that of the first channel and is perpendicular to the flow direction.

[0153] Clause 5. The valve as described in any one of Clauses 2 to 4, wherein the second channel is longer than the first channel.

[0154] Clause 6. A valve as described in any of the preceding clauses, wherein the compartment is deeper, wider, or both than the first passage.

[0155] Clause 7. A valve as described in any of the preceding clauses, wherein the compartment is cylindrical.

[0156] Clause 8. The valve as described in Clause 7, wherein the compartment has a circular, oval, oblong, or polygonal cross-section.

[0157] Clause 9. An apparatus comprising: a valve as described in any of the preceding clauses; and an upstream chamber wherein a portion of the upstream chamber adjacent to the first inlet of the first passage of the valve is tapered to allow a smooth transition between the upstream chamber and the first inlet of the first passage of the valve.

[0158] Clause 10. The apparatus as described in Clause 9, wherein the tapering portion of the upstream chamber has a trapezoidal cross-section parallel to the flow direction.

[0159] Clause 11. The device as described in any one of Clauses 9 to 10, wherein the tapering portion of the upstream chamber is configured at least in part based on the fluid to be processed by the device.

[0160] Clause 12. The apparatus of any one of Clauses 9 to 11, wherein the tapering portion of the upstream chamber has an angle of about -10 to -30 degrees, about -30 to -60 degrees, or about -60 to -80 degrees relative to the first channel.

[0161] Clause 13. An apparatus comprising: a rotation axis; and a channel for transferring fluid by rotating the apparatus about the rotation axis, the channel including an inlet, an outlet located radially outside the inlet relative to the rotation axis, and a first portion between the inlet and the outlet; and a structure connected to a first side of the first portion of the channel and configured to: (i) allow the transfer of the fluid when the apparatus rotates at a first speed; (ii) collect fluid residue when the apparatus rotates at a second speed greater than the first speed; and (iii) retain the collected fluid residue within the structure when the apparatus is subjected to acceleration, deceleration, or both.

[0162] Clause 14. The apparatus as described in Clause 13, wherein the structure comprises: a recess for receiving the fluid residue; and a chamber connecting the recess to a first side of the first portion of the channel and having a greater depth than the first portion of the channel and the recess, thereby acting as a valve between the first portion of the channel and the recess.

[0163] Clause 15. The device as described in any one of Clauses 13 to 14, wherein: at least a portion of the structure is located radially outward of the first portion of the channel; and the maximum permissible level of the fluid residue is defined by the radially innermost point on the junction formed by the chamber and the first side of the first portion of the channel.

[0164] Clause 16. The apparatus as described in Clause 15, wherein the second side of the first portion of the channel is positioned radially inside the maximum permissible level of the fluid residue.

[0165] Clause 17. The device as described in any one of Clauses 13 to 16, wherein the first portion of the channel is bent.

[0166] Clause 18. An apparatus comprising: a rotation axis; and a mixing chamber having a curved side not coaxial with the rotation axis and configured for inertial mixing of fluids having two or more different components.

[0167] Clause 19. A method comprising: (A) obtaining an apparatus including a rotation axis and a mixing chamber having a curved side not coaxial with the rotation axis, wherein the mixing chamber contains a fluid comprising two or more different components; (B) accelerating the apparatus to a first velocity in a direction toward the curved side of the mixing chamber; and (C) abruptly decelerating the apparatus such that the fluid moves toward the curved side of the mixing chamber due to inertia, wherein the curved side of the mixing chamber converts the movement of the fluid into a circular motion that generates eddies, thereby promoting the mixing of the two or more different components in the fluid.

[0168] Clause 20. The method as described in Clause 19, further comprising: (D) repeating the acceleration (B) and the deceleration (C) once or more.

[0169] Clause 21. The method as described in any one of Clauses 19 to 20, wherein the deceleration (C) brings the device to a complete stop.

[0170] Clause 22. The method of any one of Clauses 19 to 21, wherein the deceleration (C) is performed at a deceleration of at least 500 rpm / s, at least 1000 rpm / s, at least 1500 rpm / s, at least 2000 rpm / s, or at least 2500 rpm / s, at least 3000 rpm / s, at least 5000 rpm / s, 10000 rpm / s, at least 50000 rpm / s, or greater.

[0171] Clause 23. The method of any one of Clauses 19 to 22, wherein the volume of said fluid is at most 50%, at most 55%, at most 60%, at most 65%, or at most 70% of said mixing chamber.

[0172] Clause 24. The method of any one of Clauses 19 to 23, wherein the first velocity is based at least in part on the type of fluid, the amount of fluid, the shape of the mixing chamber, or any combination thereof.

[0173] Clause 25. The method of any one of Clauses 19 to 24, wherein the mixing chamber includes a passage on a side opposite to the curved side and not coaxial with the axis of rotation, the method further comprising: (E) accelerating the device at a second speed in a direction toward the passage; and (F) abruptly decelerating the device such that the fluid moves toward the passage of the mixing chamber due to inertia.

[0174] Clause 26. The method as described in Clause 25, wherein the second velocity is based at least in part on the type of fluid, the amount of fluid, the shape of the mixing chamber, or any combination thereof.

[0175] Clause 27. A method comprising: (A) obtaining an apparatus having a rotation axis and a chamber having a passage not coaxial with the rotation axis, wherein the chamber contains fluid; (B) accelerating the apparatus in a direction toward the passage toward the chamber; and (C) abruptly decelerating the apparatus such that the fluid moves toward the passage of the chamber due to inertia.

[0176] Clause 28. A capillary channel comprising: an open end; a dead end positioned radially outward of the open end relative to an axis of rotation; and a first flow channel, a second flow channel, and a third flow channel, wherein the first flow channel has an inlet at the open end for receiving fluid; the third flow channel has an outlet at the open end for discharging air; and a second flow channel formed between and connected to the first and third flow channels, wherein the second flow channel has a different flow resistance than the first and third flow channels, thereby allowing the fluid to first flow from the open end through the first flow channel to the dead end, and then from the dead end through the second flow channel, the third flow channel, or both to the open end to facilitate bubble-free pre-filling.

[0177] Clause 29. The capillary channel as described in Clause 28, wherein the first channel, the second channel, and the third channel together form a stepped cross-section perpendicular to the length direction of the capillary channel.

[0178] Clause 30. The capillary channel as described in Clause 29, wherein the first and third channels are deeper than the second channel.

[0179] Clause 31. The capillary channel as described in Clause 30, wherein the first flow channel and the third flow channel are substantially identical to each other.

[0180] Clause 32. The capillary channel as described in Clause 30, wherein the first flow channel and the third flow channel are different from each other.

[0181] Clause 33. The capillary channel as described in any one of Clauses 29 to 32, wherein at least two of the first flow channel, the second flow channel, and the third flow channel have the same width.

[0182] Clause 34. The capillary channel as described in any one of Clauses 29 to 33, wherein at least two of the first flow channel, the second flow channel, and the third flow channel have different widths.

[0183] Clause 35. An apparatus comprising: a rotation axis; a ventilation port; and a capillary channel as described in any one of Clauses 28 to 34, wherein the outlet of the third flow channel of the capillary channel is connected to the ventilation port.

[0184] Clause 36. An apparatus comprising: a chamber; and a channel connected to the chamber for delivering fluid into the chamber, wherein the chamber and the channel together form a junction that minimizes or eliminates capillary flow as the fluid flows from an outlet of the channel into the chamber.

[0185] Clause 37. The device as described in Clause 36, wherein the channel includes a protrusion forming at least a portion of the engagement.

[0186] Clause 38. The device as described in Clause 37, wherein the protruding portion includes a U-shaped wall located on each side of the channel at the outlet of the channel.

[0187] Clause 39. The device as described in Clause 37, wherein the protruding portion includes a V-shaped wall located on each side of the channel at the outlet of the channel.

[0188] Clause 40. The device of any one of Clauses 36 to 39, wherein the wall of the chamber adjacent to the outlet of the channel is radially inwardly bent relative to the outlet of the channel to form at least a portion of the joint.

[0189] Clause 41. The apparatus of any one of Clauses 36 to 40, wherein: the junction allows the fluid to flow from the outlet of the channel into the chamber in the direction of centrifugal force.

[0190] Clause 42. A method comprising: (A) obtaining an apparatus comprising a structure filled with an absorbing dye, wherein the structure includes a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known; (B) measuring a first optical density of the absorbing dye at the first portion of the structure and a second optical density of the absorbing dye at the second portion of the structure; (C) calculating an optical density difference between the first optical density and the second optical density; (D) calculating a ratio of the optical density difference to the nominal depth difference, wherein the ratio represents the product of the extinction coefficient and the concentration of the absorbing dye; and (E) using the ratio to determine the first depth of the first portion of the structure, the second depth of the second portion of the structure, the depth of any additional structure of the apparatus, or any combination thereof.

[0191] Clause 43. The method as described in Clause 42, wherein the obtaining (A) comprises: obtaining the apparatus having the structure; and filling the structure with the absorbing dye.

[0192] Clause 44. An apparatus comprising: one or more structures, each structure including a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known, thereby allowing self-calibration of the depth of any structure of the apparatus independent of variations in the manufacture of the apparatus.

[0193] Clause 45. The apparatus as described in Clause 44, wherein the one or more structures include a first structure and a second structure located at different locations of the apparatus.

[0194] Clause 46. The apparatus as described in Clause 45, wherein the nominal depth difference of the first structure is the same as that of the second structure.

[0195] Clause 47. The apparatus as described in Clause 45, wherein the nominal depth difference of the first structure is different from that of the second structure.

[0196] Clause 48. A method comprising: (A) obtaining an apparatus comprising a structure located in a passage of a mixture having a first component, wherein the structure includes a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known; (B) measuring a first optical density of the first component at the first portion of the structure and a second optical density of the first component at the second portion of the structure; (C) calculating an optical density difference between the first optical density and the second optical density; and (D) determining a concentration of the first component in the mixture based at least in part on the optical density difference and the nominal depth difference.

[0197] Clause 49. The method of Clause 48, wherein the concentration of the first component in the mixture is determined by comparing the optical density difference with a calibration curve at an optical path corresponding to the nominal depth difference.

[0198] Clause 50. The method of Clause 49, further comprising: (E) creating the calibration curve prior to the determination (D), wherein the creation (E) comprises: (i) preparing a series of standard solutions having known concentrations of the first component; (ii) measuring the absorbance of each of the standard solutions at one or more specific wavelengths for the first component at one or more optical paths to obtain a plurality of absorbance values; and (iii) plotting the absorbance values ​​against the corresponding concentrations of the first component to create the calibration curve for each of the one or more optical paths.

[0199] Clause 51. The method as described in Clause 50, wherein the measurement of absorbance is performed using a spectrophotometer or a microfluidic device.

[0200] Clause 52. The method as described in Clause 48, wherein the extinction coefficient of the first component is known; and the concentration of the first component in the mixture is calculated by dividing the optical density difference by the nominal depth difference and the extinction coefficient of the first component.

[0201] Clause 53. The method as described in any one of Clauses 48 to 52, wherein the first component is hemoglobin.

[0202] Clause 54. An apparatus comprising: a structure located in a passage of a mixture having a first component, wherein the structure includes a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known, thereby allowing the concentration of the first component to be measured independently of variations in the manufacture of the apparatus.

[0203] Clause 55. A system for operating the device or performing the method as described in any of the preceding clauses.

[0204] Cited terms and references The terminology used herein is for the purpose of describing particular implementations only and is not intended to limit the claims. As used in the description of implementations and the appended claims, the singular forms “a,” “an,” “the,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should be understood that terms such as “left” or “right,” “top” or “bottom,” “lower” or “upper,” “inner” or “outer,” “inward” or “outward,” etc., are used to describe features of exemplary embodiments with reference to the location of features shown in the accompanying drawings. It should 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 “first element” and “second element” are consistently renamed.

[0205] As used herein, the term "and / or" means and covers any and all possible combinations of one or more of the associated listed items. It should also be understood that the terms "include, include, including, comprise, comprises, and / or comprising" as used in this specification specify the presence of the stated features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof.

[0206] This document uses the term "about" or "approximately" 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, an unlisted close or approximate figure may be a figure that provides a substantial equivalence to the 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, as used herein, the term "about" in conjunction with a figure 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). It should also be understood that when a numerical range is disclosed herein, any numerical values ​​falling within that range are also specifically disclosed.

[0207] As used herein, the term "if" is to be interpreted as meaning "when," "after," "in response to a determination," "in response to a detection," or "according to a determination," depending on the context. Similarly, as used herein, the terms "if determined" or "if [the condition or event] is detected" are to be 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.

[0208] When the reference numerals are given as "the", i When used in identification, this reference numeral refers to a general component, assembly, or embodiment. For example, "unit". i " refers to the first in multiple units" i unit.

[0209] All references cited in this paper are incorporated herein in their entirety and for all purposes, as if each individual publication, patent, or patent application were specifically and individually cited and incorporated herein in their entirety for all purposes.

Claims

1. A valve, the valve comprising: A first channel having a first inlet and a first outlet, wherein the first inlet is connected to an upstream chamber and has a cross-section perpendicular to the flow direction that is the same as or smaller than that of the upstream chamber, thereby forming a hydrophobic junction with the upstream chamber at the first inlet; as well as A compartment connected to the first outlet of the first channel, wherein the compartment has a cross-section perpendicular to the flow direction that is larger than the first outlet of the first channel, thereby forming a hydrophilic junction at the first outlet of the first channel.

2. The valve of claim 1, further comprising: The second channel has a second inlet and a second outlet, wherein the second inlet is connected to the compartment and the second outlet is connected to the downstream chamber.

3. The valve of claim 1, wherein the compartment is deeper, wider, or both than the first passage.

4. An apparatus comprising: The valve as described in claim 1; as well as The upstream chamber, wherein the portion of the upstream chamber adjacent to the first inlet of the first channel of the valve is tapered to allow a smooth transition between the upstream chamber and the first inlet of the first channel of the valve.

5. The apparatus of claim 4, wherein the tapering portion of the upstream chamber has a trapezoidal cross-section parallel to the flow direction.

6. An apparatus comprising: axis of rotation; as well as A channel for transferring fluid by rotating the device about the axis of rotation, the channel including an inlet, an outlet located radially outside the inlet relative to the axis of rotation, and a first portion between the inlet and the outlet; as well as A structure connected to a first side of the first portion of the channel and configured to: (i) allow the transfer of the fluid when the device rotates at a first speed; (ii) Collecting fluid residue when the device rotates at a second speed greater than the first speed; (iii) when the device is subjected to acceleration, deceleration or both, the collected fluid residue is trapped within the structure.

7. The apparatus of claim 6, wherein the structure comprises: A groove for containing the fluid residue; as well as A chamber that connects the groove to the first side of the first portion of the channel and has a greater depth than the first portion of the channel and the groove, thereby acting as a valve between the first portion of the channel and the groove.

8. The apparatus of claim 6, wherein: At least a portion of the structure is located radially outward of the first portion of the channel; and The radial innermost point on the junction formed by the first side of the first portion of the chamber and the channel defines the maximum permissible level of the fluid residue.

9. The apparatus of claim 8, wherein the second side of the first portion of the channel is positioned radially inside the maximum permissible level of the fluid residue.

10. The apparatus of claim 6, wherein the first portion of the channel is bent.

11. A method, the method comprising: (A) A receiving device comprising a rotating axis and a mixing chamber having a curved side not coaxial with the rotating axis, wherein the mixing chamber contains a fluid comprising two or more different components; (B) Accelerate the device to a first speed in the direction toward the curved side of the mixing chamber; and (C) The device is suddenly decelerated, causing the fluid to move toward the curved side of the mixing chamber due to inertia, wherein the curved side of the mixing chamber converts the movement of the fluid into a circular motion that generates eddies, thereby promoting the mixing of the two or more different components in the fluid.

12. The method of claim 11, further comprising: (D) Repeat the acceleration (B) and deceleration (C) once or more.

13. The method of claim 12, wherein the mixing chamber includes a passageway on a side opposite to the curved side and not coaxial with the axis of rotation, the method further comprising: (E) Accelerate the device at a second speed in the direction toward the passage; as well as (F) The device is suddenly decelerated, causing the fluid to move toward the passage of the mixing chamber due to inertia.

14. A method, the method comprising: (A) A receiving device having a rotation axis and a chamber having a passage that is not coaxial with the rotation axis, wherein the chamber contains fluid; (B) Accelerate the device in the direction of the passage toward the chamber; as well as (C) The device is suddenly decelerated, causing the fluid to move toward the passage of the chamber due to inertia.

15. A capillary channel, said capillary channel comprising: Open end; Dead end, which is positioned radially outside the opening end relative to the axis of rotation; as well as The first flow channel, the second flow channel, and the third flow channel, among which The first flow channel has an inlet at the open end for receiving fluid; The third flow channel has an outlet at the opening end for air discharge; and The second flow channel is formed between and connected to the first and third flow channels, wherein the second flow channel has a different flow resistance than the first and third flow channels, thereby allowing the fluid to flow first from the open end through the first flow channel to the dead end, and then from the dead end through the second flow channel, the third flow channel, or both to the open end to facilitate bubble-free pre-filling.

16. The capillary channel of claim 15, wherein the first flow channel, the second flow channel and the third flow channel together form a stepped cross-section perpendicular to the length direction of the capillary channel.

17. The capillary channel of claim 16, wherein the first flow channel and the third flow channel are deeper than the second flow channel.

18. An apparatus comprising: Chamber; as well as A channel connected to the chamber for delivering fluid into the chamber, wherein the chamber and the channel together form a junction that minimizes or eliminates capillary flow as the fluid flows from the outlet of the channel into the chamber.

19. The apparatus of claim 18, wherein the channel includes a protrusion forming at least a portion of the engagement.

20. The apparatus of claim 19, wherein the protruding portion includes a U-shaped or V-shaped wall located on each side of the channel at the outlet of the channel.

21. The apparatus of claim 20, wherein the wall of the chamber adjacent to the outlet of the channel is radially inwardly bent relative to the outlet of the channel to form at least a portion of the joint.

22. The apparatus of claim 21, wherein: The junction allows the fluid to flow from the outlet of the channel into the chamber in the direction of centrifugal force.

23. A method, the method comprising: (A) A obtaining apparatus comprising a structure filled with an absorbent dye, wherein the structure comprises a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known; (B) Measure the first optical density of the absorbing dye at the first portion of the structure and the second optical density of the absorbing dye at the second portion of the structure; (C) Calculate the optical density difference between the first optical density and the second optical density; (D) Calculate the ratio of the optical density difference to the nominal depth difference, wherein the ratio represents the product of the extinction coefficient and concentration of the absorbing dye; as well as (E) Use the ratio to determine the first depth of the first portion of the structure, the second depth of the second portion of the structure, the depth of any additional structure of the device, or any combination thereof.

24. The method of claim 23, wherein obtaining (A) comprises: Obtain the apparatus having the aforementioned structure; as well as The structure is filled with the absorbent dye.

25. An apparatus comprising: One or more structures, each structure including a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but the nominal depth difference between the first depth and the second depth is known, thereby allowing self-calibration of the depth of any structure of the device independent of variations in the manufacture of the device.

26. The apparatus of claim 25, wherein the one or more structures include a first structure and a second structure located at different positions in the apparatus.

27. A method, the method comprising: (A) A obtaining apparatus comprising a structure located in a passage of a mixture having a first component, wherein the structure comprises a first portion having a first depth and a second portion having a second depth, wherein the first depth and the second depth are different from each other, but a nominal depth difference between the first depth and the second depth is known; (B) Measure the first optical density of the first component at the first portion of the structure and the second optical density of the first component at the second portion of the structure; (C) Calculate the optical density difference between the first optical density and the second optical density; as well as (D) The concentration of the first component in the mixture is determined at least in part based on the optical density difference and the nominal depth difference.

28. The method of claim 27, wherein the concentration of the first component in the mixture is determined by comparing the optical density difference with a calibration curve at an optical path corresponding to the nominal depth difference.

29. The method of claim 28, further comprising: (E) Create the calibration curve prior to the determination (D), wherein the creation (E) includes: (i) Prepare a series of standard solutions having known concentrations of the first component; (ii) Measuring the absorbance of each of the standard solutions at one or more specific wavelengths for the first component at one or more optical pathways to obtain multiple absorbance values; and (iii) Plot the absorbance values ​​against the corresponding concentrations of the first component to create the calibration curve for each of the one or more optical paths.

30. The method of claim 27, wherein: The extinction coefficient of the first component is known; and The concentration of the first component in the mixture is calculated by dividing the optical density difference by the nominal depth difference and the extinction coefficient of the first component.

31. The capillary channel of any one of claims 15 to 17, comprising a biological sample comprising a mixture of aqueous and non-aqueous biological components, moved from the input port to the outer measurement chamber by inertial and centrifugal forces for analysis and evaluation.

32. The capillary channel of claim 31, wherein the mixture is a mixture of body fluids and cells.

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