Microfluidic Sample Handling

Abstract

Structures, devices and methods for handling fluids are provided. A valve includes a first channel having a first inlet connected to an upstream chamber. The first inlet of the first channel has a cross-section perpendicular to a 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 channel. The compartment has a cross-section perpendicular to the flow direction that is larger than the first outlet of the first channel, and thus forms a hydrophilic junction at the first outlet of the first channel.

Description

Microfluidic Sample Handling FIELD OF TECHNIQUE

[0001] This application claims priority over 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. FIELD OF TECHNIQUE

[0002] This disclosure relates to devices and methods for handling fluids and, in particular, to devices and methods for handling fluids in microfluids. FUNDAMENTALS

[0003] Currently, 70% of all medical decisions depend on laboratory-based diagnoses, but today, the diagnostic process is disconnected from how care is delivered. The primary care system requires patients to travel to external phlebotomy sites to have blood collected, which is then mailed to laboratories and processed overnight. This means that laboratory results reach healthcare professionals long after the patient has left. This friction in care delivery and disease management leads to tremendous waste in the healthcare system: a. Patients often delay undergoing laboratory testing or fail to adhere to laboratory tests or subsequent care recommendations. b. The gap in the diagnostic process leads to missed tests, missed diagnoses, lack of intervention, and ultimately, poor outcomes. c. Healthcare professionals waste time tracking down lab orders and patient consultation notes. When intervention is needed, even more time is wasted reaching patients and conducting subsequent steps in the patient care pathway. Petition 870250101783, dated 06 / 11 / 2025, page 5 / 110 2 / 67

[0004] These problems are even more serious when caring for rural populations or patients belonging to groups facing adverse social determinants of health, where there are many challenges to ensuring successful follow-up from an initial consultation with the patient.

[0005] Several companies have built point-of-care instruments to overcome this division. However, these instruments are limited to single types of tests and cannot fully meet the workflow needs of primary care providers for a single system that produces simple, comprehensive, and rapid test results. A product to meet these needs is currently under development. It achieves this through a highly automated workflow enabled by the use of centrifugal microfluidic discs.

[0006] Centrifugal microfluidics are used in clinical chemistry, immunoassays, hematology, medicine, biomedical research, and other fields. These applications often require fluid measurement, transfer, mixing, and / or other processes. Many of these applications also require the detection of concentrations and reactions. However, achieving effective control in the dosing, transfer, and mixing of fluids and precise measurement of concentrations and reactions can be a challenge in microfluidics because the behavior of liquids can be significantly different from their bulk counterparts due to the small scales involved.

[0007] Consequently, there remains a need for improved devices and methods in centrifugal microfluidics to address these and other needs in the art. SUMMARY

[0008] In a first aspect, the present disclosure provides a simple and reliable valve that integrates hydrophobic and hydrophilic principles into a single simple structure and eliminates the need for surface treatments. The valve includes a first channel and a compartment. The first Petition 870250101783, dated 06 / 11 / 2025, page 6 / 110 3 / 67 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 a flow direction that is the same as or smaller than the upstream chamber, thus 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, thus 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 of these embodiments, the compartment has a circular, oval, oblong, or polygonal cross-section.

[0010] In some embodiments, the valve also 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 one 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 present disclosure provides a device including a valve disclosed in this document and an upstream chamber. In some embodiments, a portion of the upstream chamber adjacent to the first inlet of the valve's first channel is tapered to smooth the transition between the upstream chamber and the first inlet of the valve's first channel.

[0012] In some of these 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 based, at least in part, on a fluid to be processed by Petition 870250101783, dated 06 / 11 / 2025, p. 7 / 110 4 / 67 device. In some embodiments, the conical 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, the present disclosure provides a device with a structure for trapping the remaining fluid. The device is rotational about an axis of rotation. The device includes a channel for transferring a fluid by rotating the device about the axis of rotation. The channel includes an inlet, an outlet radially outward from the inlet relative to the axis of rotation, and a first portion between the inlet and the outlet. The device also includes a structure connected to a first side of the first portion of the channel. The structure is configured to (i) allow fluid transfer when the device rotates at a first speed, (ii) collect residual fluid when the device rotates at a second speed that is greater than the first speed, and (iii) trap the collected residual fluid within the structure when the device is subjected to acceleration, deceleration, or both.

[0014] In some embodiments, the structure includes a bag to contain the residual fluid and a chamber connecting the bag to the first side of the first portion of the channel. The chamber has a greater depth than the first portion of the channel and the compartment, thus acting as a valve between the first portion of the channel and the compartment.

[0015] In some embodiments, at least one portion of the structure is positioned radially outward from the first portion of the channel, and a radially more inward point at a junction formed by the chamber and the first side of the first portion of the channel defines a maximum allowable level for fluid residue. In some embodiments, a second side of the first portion of the channel is positioned radially inward from the maximum allowable level for fluid residue. In some embodiments, the first portion of the channel is folded.

[0016] In a fourth aspect, the present disclosure provides a Petition 870250101783, dated 06 / 11 / 2025, p. 8 / 110 5 / 67 device for mixing a fluid with two or more different components by inertia. The device is rotational around an axis of rotation. The device includes a mixing chamber having a curved side that is not coaxial with the axis of rotation and configured to mix a fluid with two or more different components by inertia.

[0017] In a fifth aspect, the present disclosure provides a method for mixing a fluid with two or more different components by inertia. The method includes (A) obtaining a device including a rotating axis and a mixing chamber with a curved side that is not coaxial with the rotating axis, wherein the mixing chamber contains a fluid including two or more different components. In some embodiments, a volume of the fluid is at most 50%, at most 55%, at most 60%, at most 65%, or at most 70% of the mixing chamber.

[0018] The method also 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 a type of fluid, a quantity of fluid, a shape of the mixing chamber, or any combination thereof.

[0019] The method also includes (C) abruptly decelerating the device so that the fluid moves toward the curved side of the mixing chamber due to inertia. The curved side of the mixing chamber translates the fluid motion into a circular motion that produces vortices, thus promoting the mixing of the two or more different components in the fluid. In some embodiments, the deceleration (C) is performed at a speed 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 higher. In some embodiments, the deceleration (C) causes the device to stop completely.

[0020] In some modalities, the method also includes (D) repeating the Petition 870250101783, dated 06 / 11 / 2025, p. 9 / 110 6 / 67 acceleration (B) and deceleration (C) one or more times.

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

[0022] In a sixth aspect, the present disclosure provides a method for directing fluid flow by inertia. The method includes (A) obtaining a device having an axis of rotation and a chamber having a path that is not coaxial with the axis of rotation, wherein the chamber contains a fluid, (B) accelerating the device in a direction towards the chamber path, and (C) abruptly decelerating the device so that the fluid moves towards the chamber path due to inertia.

[0023] In a seventh aspect, the present disclosure provides a capillary channel capable of bubble-free initiation. The capillary channel includes an open end and a dead end positioned radially outward from the open end relative to an axis of rotation. The capillary channel also includes the first, second, and third lanes. The first lane has an inlet at the open end to receive a fluid. The third lane has an outlet at the open end to vent air. The second lane is formed between and connected to the first and third lanes. The second lane has a different flow resistance than the first and third lanes, thus allowing the fluid to flow first through the first lane from the open end to the dead end and then flow through the second lane, the third lane, or both from the dead end to the open end to facilitate bubble-free initiation. Petition 870250101783, dated 06 / 11 / 2025, page 10 / 110 7 / 67

[0024] In some modalities, the first, second, and third lanes collectively form a stepped cross-section perpendicular to a length direction of the capillary channel. In some modalities, the first and third lanes are deeper than the second lane. In one modality, the first and third lanes are substantially the same as each other. In another modality, the first and third lanes are different from each other. In some modalities, at least two of the first, second, and third lanes have the same width. In some modalities, at least two of the first, second, and third lanes have a different width.

[0025] In an eighth aspect, the present disclosure provides a rotating device around an axis of rotation. The device includes a vent port and a capillary channel disclosed in this document. The capillary is positioned radially outward from the vent port, with the outlet of the third track of the capillary channel connected to the vent port.

[0026] In a ninth aspect, the present disclosure provides a device with a compressed structure for directing fluid flow. The device includes a chamber and a channel connected to the chamber to distribute a fluid to the chamber. The chamber and channel collectively form a junction that minimizes or eliminates capillary flow when the fluid exits from a channel outlet into the chamber. In some embodiments, the junction allows the fluid to flow from the channel outlet into the chamber in a direction of centrifugal force.

[0027] In some embodiments, the canal includes a protruding portion that forms at least a portion of the junction. In one embodiment, the protruding portion includes a U-shaped wall on each side of the canal at the canal outlet. In another embodiment, the protruding portion includes a V-shaped wall on each side of the canal at the canal outlet. In some embodiments, a chamber wall adjacent to the canal outlet is radially curved inward relative to the canal outlet to form at least a portion of the junction.

[0028] In a ninth aspect, the present disclosure provides a method for measuring depths with self-calibration capability. The method Petition 870250101783, dated 06 / 11 / 2025, p. 11 / 110 8 / 67 includes (A) obtaining a device including a structure filled with an absorbent dye. The structure includes a first portion having a first depth and a second portion having a second depth. The first and second depths are different from each other, but the nominal depth difference between the first and second depths is known. In some embodiments, obtaining (A) includes obtaining the device with the structure and filling the structure with the absorbent dye.

[0029] The method also includes (B) measuring a first optical density of the absorbing dye in the first portion of the structure and a second optical density of the absorbing dye in the second portion of the structure and (C) calculating an optical density difference between the first and second optical densities. The method further includes (D) calculating a ratio of the optical density difference to the nominal depth difference. The ratio represents a product of an extinction coefficient and a concentration of the absorbing dye. In addition, 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, a depth of any additional structure of the device, or any combination thereof.

[0030] In a tenth aspect, the present disclosure provides a device for measuring depths with self-calibration capability. The device includes one or more structures, each including a first portion having a first depth and a second portion having a second depth. The first and second depths are different from each other, but a nominal depth difference between the first and second depths is known, thus allowing self-calibration of a depth of any device structure independently of variations in the manufacture of the device.

[0031] In some embodiments, one or more structures include a first structure and a second structure in different locations of the device. In one embodiment, the nominal depth difference of Petition 870250101783, dated 06 / 11 / 2025, p. 12 / 110 9 / 67 The first structure is the same as the second structure. In another configuration, the nominal depth difference between the first structure and the second structure is different.

[0032] In an eleventh aspect, the present disclosure provides a method for measuring concentration despite manufacturing variability. The method includes (A) obtaining a device including a structure located in a path 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known. In some embodiments, the first component is hemoglobin.

[0033] The method also includes (B) measuring a first optical density of the first component in the first portion of the structure and a second optical density of the first component in 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 an optical density difference between the first and second optical densities 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. In some embodiments, the concentration of the first component in the mixture is determined by comparing the optical density difference with a calibration curve on an optical path corresponding to the nominal depth difference. In some embodiments, an 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 also includes (E) creating, before the determination (D), the calibration curve. In some embodiments, the Petition 870250101783, dated 06 / 11 / 2025, p. 13 / 110 10 / 67 creation (E) includes (i) preparing a series of standard solutions with 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 in one or more optical pathways, thus obtaining 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 pathways.

[0036] In a twelfth aspect, the present disclosure provides a device for measuring concentration despite manufacturing variability. The device includes a structure located in a path 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known, thus allowing the measurement of a concentration of the first component independently of variations in the manufacture of the device.

[0037] The devices, systems and methods of the present disclosure have other features and advantages that will be evident from, or are set forth in more detail in, the accompanying figures, which are incorporated herein, and in the following Detailed Description, which together serve to explain certain exemplary embodiments of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The accompanying Figures, which are incorporated into and form part of this descriptive report, illustrate one or more exemplary embodiments of the present disclosure and, together with the Detailed Description, serve to explain the principles and implementations of exemplary embodiments of the invention. The accompanying Figures are not necessarily to scale. The specific design features of the present invention as disclosed in this document, including, for example, dimensions, orientations, Petition 870250101783, dated 06 / 11 / 2025, page 14 / 110 11 / 67 specific locations and formats will be determined in part by the particular application environment and intended use. Furthermore, the components illustrated in the figures are combinable in any useful number and combination.

[0039] In the Figures:

[0040] FIG. 1A is a schematic diagram illustrating a device including a valve, wherein the valve is in a hydrophobic setting, according to some exemplary embodiments of the present disclosure;

[0041] FIG. 1B is a schematic diagram illustrating the device of FIG. 1A, in which the valve is in a hydrophilic setting, according to an exemplary embodiment of the present disclosure;

[0042] FIG. 1C is a schematic diagram illustrating a cross-sectional view of the device taken along the dotted line in FIG. 1A;

[0043] FIG. 1D is a schematic diagram illustrating a cross-sectional view of the device according to an alternative exemplary embodiment of the present disclosure;

[0044] FIG. 1E is a schematic diagram illustrating an existing hydrophobic valve;

[0045] FIG. 1F is a schematic diagram illustrating an existing hydrophilic valve;

[0046] FIG. 2A is an image showing a device with a structure for trapping the remaining fluid according to some exemplary embodiments of the present disclosure;

[0047] FIG. 2B is a schematic diagram illustrating a structure for trapping the remaining fluid according to some exemplary embodiments of the present disclosure;

[0048] FIG. 2C is a cross-sectional view taken along the vertical line in FIG. 2B;

[0049] FIG. 2D is an image showing a device without the structure to trap the remaining fluid; Petition 870250101783, dated 06 / 11 / 2025, p. 15 / 110 12 / 67

[0050] FIG. 3 is a flowchart illustrating a method for mixing a fluid with two or more different components by inertia according to some exemplary embodiments of this disclosure;

[0051] FIG. 4A is an image showing a device for mixing a fluid with two or more different components by inertia according to an exemplary embodiment of this disclosure;

[0052] FIG. 4B is an image showing a device for mixing a fluid with two or more different components by inertia according to an alternative exemplary embodiment of this disclosure;

[0053] FIG. 4C is an image showing a device for mixing a fluid with two or more different components by inertia according to another alternative exemplary embodiment of this disclosure;

[0054] FIG. 4D is an image showing a device for mixing a fluid with two or more different components by inertia according to yet another alternative exemplary embodiment of the present disclosure;

[0055] FIG. 5 is a flowchart illustrating a method for directing fluid flow by inertia according to some exemplary embodiments of the present disclosure;

[0056] FIG. 6 is an image showing a device for directing fluid flow by inertia according to some exemplary embodiments of the present disclosure;

[0057] FIG. 7A is an image showing a device with a capillary channel capable of bubble-free preparation according to some exemplary embodiments of the present disclosure;

[0058] FIG. 7B is a cross-sectional view illustrating the capillary channel of FIG. 7A according to some exemplary embodiments of the present disclosure;

[0059] FIG. 8A is an image showing a device with a clamped structure for directing fluid flow, according to some Petition 870250101783, dated 06 / 11 / 2025, p. 16 / 110 13 / 67 examples of the present disclosure;

[0060] FIG. 8B is a schematic diagram illustrating the compressed structure of FIG. 8A according to an exemplary embodiment of the present disclosure;

[0061] FIG. 8C is a schematic diagram illustrating the compressed structure of FIG. 8A according to an alternative exemplary embodiment of the present disclosure;

[0062] FIGS. 8D and 8E are images showing devices without a compressed structure to direct fluid flow;

[0063] FIG. 9 is a flowchart illustrating a method for measuring depths with self-calibration capability according to some exemplary embodiments of this disclosure;

[0064] FIG. 10A is an image showing a device with a structure for measuring depths with self-calibration capability according to some exemplary embodiments of the present disclosure;

[0065] FIG. 10B is a cross-sectional view illustrating the structure of FIG. 10A according to some exemplary embodiments of the present disclosure;

[0066] FIG. 11 is a flowchart illustrating a method for measuring concentration despite manufacturing variability according to some exemplary embodiments of the present disclosure;

[0067] FIG. 12A is an image showing a device with a structure for measuring concentration despite the manufacturing variability according to some exemplary embodiments of the present disclosure;

[0068] FIG. 12B is a cross-sectional view illustrating the structure of FIG. 12A according to some exemplary embodiments of the present disclosure;

[0069] FIG. 13 is a schematic diagram illustrating a device (e.g., a disk) according to some exemplary embodiments of the present disclosure; Petition 870250101783, dated 06 / 11 / 2025, p. 17 / 110 14 / 67

[0070] FIG. 14 is a schematic diagram illustrating a device (e.g., a disk) according to some exemplary embodiments of the present disclosure;

[0071] FIG. 15 is a block diagram illustrating a workflow according to some exemplary embodiments of the present disclosure;

[0072] FIG. 16A-1 is a schematic diagram and FIG. 16A-2 is a photograph illustrating a buffer loading process according to some exemplary embodiments of this disclosure;

[0073] FIG. 16B-1 is a schematic diagram and FIG. 16B-2 is a photograph illustrating a sample loading process according to some exemplary embodiments of this disclosure;

[0074] FIG. 16C-1 is a schematic diagram and FIG. 16C-2 is a photograph illustrating a buffer overflow process according to some exemplary embodiments of this disclosure;

[0075] FIG. 16D-1 is a schematic diagram and FIG. 16D-2 is a photograph illustrating a sample overflow process according to some exemplary embodiments of the present disclosure;

[0076] FIG. 16E-1 is a schematic diagram and FIG. 16E-2 is a photograph illustrating a sample measurement process according to some exemplary embodiments of this disclosure;

[0077] FIG. 16F-1 is a schematic diagram and FIG. 16F-2 is a photograph illustrating a buffer measurement process according to some exemplary embodiments of this disclosure;

[0078] FIG. 16G-1 is a schematic diagram and FIG. 16G-2 is a photograph illustrating a rotational acceleration process according to some exemplary embodiments of the present disclosure;

[0079] FIG. 16H-1 is a schematic diagram and FIG. 16H-2 is a photograph illustrating a mixing process according to some exemplary embodiments of the present disclosure; Petition 870250101783, dated 06 / 11 / 2025, p. 18 / 110 15 / 67

[0080] FIG. 16I-1 is a schematic diagram and FIG. 16I-2 is a photograph illustrating a first measurement process according to some exemplary embodiments of this disclosure;

[0081] FIG. 16J-1 is a schematic diagram and FIG. 16J-2 is a photograph illustrating a second measurement process according to some exemplary embodiments of this disclosure;

[0082] FIG. 16K-1 is a schematic diagram and FIG. 16K-2 is a photograph illustrating a third measurement process according to some exemplary embodiments of the present disclosure;

[0083] FIG. 16L-1 is a schematic diagram and FIG. 16L-2 is a photograph illustrating a sample separation process according to some exemplary embodiments of the present disclosure; and

[0084] FIG. 16M-1 is a schematic diagram and FIG. 16M-2 and FIG. 16M-3 are photographs illustrating a self-calibration process according to some exemplary embodiments of the present disclosure. DETAILED DESCRIPTION

[0085] Simplified and Reliable Valve Design.

[0086] Microfluidic systems generally require the use of valves to regulate fluid flow, but existing solutions have limitations, such as the need for multiple components, complex manufacturing processes, or surface treatments. For example, known solutions often require multiple components and complex manufacturing processes, which can increase the cost and complexity of device fabrication. Furthermore, known solutions often require surface treatments, such as coatings, to achieve the hydrophobicity or hydrophilicity necessary for proper valve performance. These treatments can add an additional step to the manufacturing process and limit the range of materials that can be used. Additionally, known solutions are frequently limited in their applicability to certain materials or environmental conditions and may only function well with... Petition 870250101783, dated 06 / 11 / 2025, page 19 / 110 16 / 67 hydrophobic or hydrophilic materials may be sensitive to changes in temperature or humidity. Furthermore, known solutions often lack means to prevent sample drying (e.g., blood drying) and / or cell sedimentation, which can cause blockage of microfluidic channels.

[0087] Hydrophobic materials repel water and do not allow it to spread over their surfaces, while hydrophilic materials attract water and allow it to spread over their surfaces. This results in the behavior where a liquid 102 would stop at the entrance of a narrow hydrophobic plaster in a channel as illustrated in FIG. 1E and would stop at the widening of a capillary channel if it is hydrophilic as illustrated in FIG. 1F.

[0088] Hydrophobic valves rely on the interaction between the liquid and the valve disc material to control the flow of liquid through a microfluidic channel. They are typically made of hydrophobic materials, such as certain plastics, to prevent the liquid from wetting the valve surface. A hydrophobic valve typically includes a constriction or hydrophobic patch in the channel, which creates a pressure drop that prevents liquid from flowing through the valve. To open the valve, the liquid pressure must be increased beyond a certain limit to overcome the pressure drop and allow the liquid to flow through the valve. One advantage of hydrophobic valves is that they do not require surface treatments, such as hydrophobic coatings, to maintain their hydrophobicity. This makes them more economical and easier to use than other types of valves, especially for large-scale production.Furthermore, hydrophobic materials are relatively inert and chemically resistant, making them suitable for use in a wide range of applications, including those involving aggressive or corrosive liquids.

[0089] In the case of a hydrophilic material, the liquid would spread and wet the surface, which would increase the total surface area in contact with the air, reducing the pressure and causing the liquid to rise through the channel. As Petition 870250101783, dated 06 / 11 / 2025, page 20 / 110 17 / 67 Hydrophilic valves utilize the phenomenon of liquid meniscus fixation to control liquid flow through microfluidic channels. When a liquid comes into contact with a solid surface, it forms a meniscus that can be held at the point of maximum curvature, preventing further flow. By carefully designing the channel dimensions and geometry, the burst pressure can be controlled, and the valve can be actuated to open or close when the pressure exceeds a certain limit. The burst pressure is determined by several factors, including channel dimensions, surface tension, and the liquid contact angle. The smaller the channel dimensions, the greater the surface tension required to hold the liquid meniscus. Conversely, a larger channel will require less surface tension to hold the meniscus.The contact angle of the liquid is also important because it determines how much the liquid will wet the channel surface, which in turn affects the strength of the liquid-solid interaction. Hydrophilic valves have numerous important applications in microfluidic and lab-on-a-chip devices, where they are used to precisely control liquid flow and handle small fluid volumes.

[0090] The stability of hydrophobic and hydrophilic valves can be affected by changes in the hydrophobicity or hydrophilicity of the materials used to make the valve, which can cause the valves to become less effective or even fail completely.

[0091] This disclosure addresses these and / or other needs by providing a simple valve that is more effective and reliable in controlling fluid flow, especially fluids containing blood. The simple valve of this disclosure integrates hydrophobic and hydrophilic principles into a single simple structure and eliminates the need for surface treatments. This makes it easier and more economical to manufacture microfluidic devices and provides improved reliability and performance. In some embodiments, the simple valve of this disclosure includes sections designed to prevent fluid drying and cell sedimentation, which helps ensure reliable valve performance even with thicker materials (e.g., Petition 870250101783, dated 06 / 11 / 2025, page 21 / 110 18 / 67 thicker blood materials).

[0092] With reference now to FIGS. 1A-1C, a device 100 is shown according to some embodiments of the present disclosure. The device 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 generally includes a first channel 140 and a compartment 150. The first channel and the compartment are configured so that the first channel forms a hydrophobic junction with the upstream chamber, for example, functioning as a hydrophobic valve, and the compartment forms a hydrophilic junction with the first channel, for example, functioning as a hydrophilic valve.

[0093] 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 equal to or smaller than the upstream chamber. As such, it forms a hydrophobic junction with the upstream chamber to stop a fluid at the first inlet of the first channel if it 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 the first outlet of the first channel. As such, it forms a hydrophilic junction to stop a fluid at the first outlet of the first channel if it 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.

[0094] Because the 130 valve integrates hydrophobic and hydrophilic principles into a single structure, it is more stable and reliable with a wider operating range. For example, it can regulate liquid flow even if one of the characteristics is compromised. This can help increase the overall reliability and stability of the valve and extend its operating range. Petition 870250101783, dated 06 / 11 / 2025, page 22 / 110 19 / 67 The combination of hydrophobic and hydrophilic characteristics in a single valve improves performance and allows for a wider operating range compared to traditional hydrophobic or hydrophilic valves. Furthermore, it allows for the optimization of one or more dimensions (e.g., length, width, height) of the first channel and / or compartment, without any surface standardization, to ensure reliable valve operation under both types of conditions. For example, in some specific implementations, the first channel may have a width of 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 first canal may have a depth of 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 first channel may have a length of 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, the present disclosure is not limited to this. For example, depending on the applications, the first channel may be smaller, shorter, larger, or longer. It may have a width or depth that is 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. It may have a length that is 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.

[0095] Valve 130 may include additional, optional or alternative features. For example, in some embodiments, valve 130 includes a second channel 160 configured to prevent sample drying. In some embodiments, the second channel 160 connects the compartment to the downstream chamber, for example, having a second inlet 161 connected to the compartment and a second outlet 162 connected to the downstream chamber.

[0096] The addition of a second channel can help minimize sample evaporation (e.g., blood), surface hydration, and / or Petition 870250101783, dated 06 / 11 / 2025, page 23 / 110 20 / 67 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 clogging, surface contaminant formation, and sample quality degradation. For example, blood drying is a major problem in blood analysis applications. Drying can lead to the formation of a barrier by red blood cells, causing valve malfunction and potentially affecting analysis accuracy. A second channel can help reduce these effects by providing a longer and more restricted path for the sample, which reduces sample exposure to air and other environmental factors. This can help decrease the rate of surface evaporation and hydration and prevent moisture condensation formation, thus helping to preserve sample integrity and quality.Carefully controlling the sample's exposure to the environment is crucial for the overall performance and reliability of the system.

[0097] The second channel can be configured in the same way as the first channel or differently from the first channel. For example, in some embodiments, the second channel has a cross-section (e.g., width and depth) perpendicular to the flow direction, the same as the first channel. Alternatively, in some embodiments, the second channel has a cross-section perpendicular to the flow direction that is different from the first channel. In some typical embodiments, the second channel is longer than the first channel.

[0098] The optimization of the length, width, and / or depth of the second channel may depend on whether or not the channel is blocked after evaporation. In some embodiments, the length-to-width and length-to-depth ratios 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 second channel has a length of approximately 1 mm to 5 mm and a width or depth of approximately Petition 870250101783, dated 06 / 11 / 2025, p. 24 / 110 21 / 67 from 150 μm to about 400 μm. However, the present disclosure is not limited to this. For example, depending on the applications, the length of the second channel can reach several centimeters or more.

[0099] With reference to FIG. 1D, in 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 blockages due to cell sedimentation. For example, in some of these embodiments, a portion 112 of the upstream chamber 110 adjacent to the first inlet of the first valve channel is tapered to smooth the transition between the upstream chamber and the first inlet of the first valve channel. 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 based, at least in part, on the fluid 102 to be processed by the device. In some embodiments, the conical portion of the upstream chamber has an angle of approximately -10 to -30 degrees, approximately -30 to -60 degrees, or approximately -60 to -80 degrees relative to the first channel.However, the present disclosure is not limited to this. Depending on the applications (e.g., the fluid to be processed), portion 112 of the upstream chamber 110 may have different shapes, sizes and / or angles.

[0100] The design of the junction between the upstream chamber (e.g., a blood sample compartment) and the valve inlet can play a critical role in preventing channel blockages due to cell sedimentation. For example, using a trapezoidal shape as illustrated in FIG. 1D, as opposed to a rectangular shape illustrated in FIG. 1C, at the junction can help reduce the likelihood of channel blockage by reducing the sharpness of the transition between the upstream chamber and the first channel. The trapezoidal shape provides a smoother transition between the two parts and thus reduces the risk of cells becoming trapped or sedimented at the junction, which can cause blockages. This can help improve the overall performance and reliability of the valve, maintain sample flow through the channel, and ensure Petition 870250101783, dated 06 / 11 / 2025, page 25 / 110 22 / 67 that the valve functions as intended, even with thicker blood materials.

[0101] The valve of the present disclosure has a number of advantages over existing solutions. For example, regarding complexity, existing solutions often require multiple components, complex manufacturing processes, or surface treatments, which increases the complexity of the microfluidic device and makes it more difficult to manufacture and maintain. The valve of the present disclosure integrates hydrophobic and hydrophilic principles into a single simple structure and thus reduces the number of components and manufacturing steps required. Regarding reliability, existing solutions may not be reliable enough for certain applications, as they may become inefficient if the surface or sample properties change or if there is a delay between the time the sample hits the valve and the time the sample passes through the valve.The valve of this disclosure combines simple sections into a single structure, thus enabling the valve to function more reliably across a wider range of materials, samples, and environmental conditions. The cost of reclassification, surface treatments, and complex manufacturing processes can be expensive, making the production of existing microfluidic devices prohibitively costly for some applications. The valve of this disclosure eliminates the need for surface treatments and thus reduces the manufacturing cost of microfluidic devices. Furthermore, the passive nature of the valve, actuated 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 manufacturing cost of fluidic devices.Regarding evaporation and cell sedimentation, existing solutions may not be effective in preventing sample drying (e.g., blood drying) or cell sedimentation, which can result in valve malfunction. The valve or device of this disclosure includes features (e.g., the second channel and a... Petition 870250101783, dated 06 / 11 / 2025, page 26 / 110 23 / 67 tapered portion of the upstream chamber) to prevent evaporation and cellular sedimentation, ensuring reliable valve performance even with thicker blood materials. Furthermore, the valve and device of this disclosure allow for flexibility in material selection. The ability to use a wide range of materials for cartridge fabrication, including hydrophobic and hydrophilic materials, opens new possibilities for the design and manufacture of fluidic devices. The valve and device of this disclosure can be adapted to different environmental conditions, such as temperature and humidity, and used in a wide range of applications.

[0102] Overall, the present disclosure provides a more effective solution for controlling fluid flow in microfluidic devices by simplifying device design, improving reliability, reducing cost, and preventing evaporation and cell sedimentation. The combination of these design features makes the valve and device of the present disclosure a significant advancement in the field of microfluidic and fluidic devices, offering potential benefits for a wide range of applications, including but not limited to biomedical and clinical applications.

[0103] Structure to trap the remaining fluid.

[0104] In many applications, the remaining fluid (e.g., blood) 204 would be temporarily accumulated, for example, at the bottom of a U-shaped channel, as illustrated in FIG. 2D. The remaining fluid, however, is not completely trapped and would be drawn into a downstream chamber (e.g., a measuring chamber) in subsequent processes due to its high viscosity and / or other factors. Furthermore, the temporarily accumulated fluid could block access to an air vent, causing negative pressure to build up, resulting in uncontrollable fluid movement. A general solution would be to add a long, deep U-shaped structure. However, there is not enough space on the disk to accommodate such a structure, and a significantly larger volume of fluid (e.g., blood) would be required. There is also a chance that, for very large samples... Petition 870250101783, dated 06 / 11 / 2025, page 27 / 110 24 / 67 thick, the drag force would not be able to pull the blood without breaking it. This can cause blockage of the channel and the buildup of negative pressure. The present disclosure addresses these and / or other needs by providing a structure that can not only trap the remaining fluid but also allow control of fluid flow.

[0105] With reference to FIGS. 2A-2C, a device 200 is shown according to some embodiments of the present disclosure. The device 200 is rotatable about an axis of rotation 202. The device includes a channel 210 for transferring a fluid by rotating the device about the axis of rotation. The channel 210 includes an inlet 211 and an outlet 212 positioned radially outward from the inlet relative to the axis of rotation. 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 in the first portion) and a second side 222 (e.g., the other side of the channel in 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 from its corresponding second side 222.In some forms, 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 canal.

[0106] The device 200 also includes a structure 230 connected to the 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., remaining fluid) when the device rotates at a second speed that is greater than the first speed, and (iii) trap the collected fluid residue within the structure when the device is subjected to acceleration, deceleration, or both.

[0107] For example, in some embodiments, structure 230 includes a bag 240 to contain the fluid residue and a chamber 250 to connect Petition 870250101783, dated 06 / 11 / 2025, page 28 / 110 25 / 67 the pouch on the first side of the first portion of the channel. The 250 chamber has a greater depth than the first portion of the channel and the pouch, thus acting as a valve between the first portion of the channel and the pouch. In some embodiments, the pouch may be shallow, narrow, and / or relatively long to keep the remaining fluid inside the pouch, even when the disc is subjected to strong acceleration and deceleration. For example, in some embodiments, the channel or pouch may have a depth of up to 1 mm, up to 1.5 mm, or up to 2 mm, and the chamber may have a depth of 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 pouch. However, the present disclosure is not limited to this. The channel, chamber, and pouch may have other shapes or dimensions and may be positioned differently.

[0108] In some embodiments, at least a portion of the structure is positioned radially outward from the first portion of the channel. For example, in some embodiments, the 240 bag or a portion of the pig is positioned radially outward from the first portion of the channel. In some embodiments, a radially more internal point at a junction formed by the chamber and the first side of the first portion of the channel defines a maximum allowable level (e.g., the dashed line in FIG. 2B) for the residual fluid. In some embodiments, the structure and / or operation are designed to ensure that the meniscus of the remaining fluid does not exceed the maximum allowable level. This allows air trapped in the bag and / or chamber to have an exit passage.

[0109] In some embodiments, the second side 222 of the first portion of the channel is positioned radially inward to the maximum permitted level for fluid residue. For example, in some embodiments, the bend on the second side of the first portion is positioned radially inward to the maximum permitted level. This prevents potential channel blockage and allows fluid transfer when needed or desired.

[0110] During centrifugation, most of the fluid (e.g., blood) will be carried downstream. However, some residue will remain in the Petition 870250101783, dated 06 / 11 / 2025, page 29 / 110 26 / 67 surfaces of the channel. These residues will be pushed past the maximum permitted level and collected at the bottom of the first portion 220 of the channel by centrifugal action. As the rotation accelerates, the centrifugal force acting on the remaining blood increases and eventually overcomes the barrier (e.g., the valve formed by the chamber 250 with the channel and / or bag) after reaching a threshold. The residues will go to the bag 240 and, in some cases, to the bottom of the bag, depending on the rotation speed, the amount of residues, the configuration of the structure and / or other factors. Subsequently, the residues will remain in the pocket even when the device is subjected to acceleration, deceleration, or both.

[0111] Inertial-Based Chamber and Mixing Method.

[0112] Mixing blood with buffer in microfluidic centrifuges can present a number of technical problems. For example, blood cells can be damaged or destroyed when subjected to high centrifugal forces, causing hemolysis (red blood cell rupture) and the release of hemoglobin into the buffer. This can interfere with downstream analysis and affect the accuracy of results. Blood can clot when it comes into contact with certain materials or surfaces, especially in microfluidic systems where there is a high surface-to-volume ratio. This can lead to blockages in the channels or cause incomplete mixing of blood with the buffer. Furthermore, achieving complete and uniform mixing of blood with buffer can be challenging in microfluidic centrifuges due to the small volumes and rapid rotation speeds involved. Incomplete mixing can result in inaccurate or unreliable results.

[0113] Existing techniques for buffered blood include those disclosed in “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 Petition 870250101783, dated 06 / 11 / 2025, page 30 / 110 27 / 67 each is incorporated herein by reference in its entirety and for all purposes. These existing techniques, however, do not provide satisfactory solutions. The present disclosure addresses these and other needs in the art, providing curvatures to the chambers and using inertial motion to create vortices to promote mixing.

[0114] With reference to FIG. 3, a flowchart is shown illustrating an exemplary method 300 for mixing a fluid according to some embodiments of the present disclosure. In the flowchart, preferred parts of the method are shown in solid-line boxes, while additional, optional or alternative parts of the method are shown in dashed-line boxes. It should be noted that the processes disclosed in this document and exemplified in the flowchart may be, but do not have to be, performed in their entirety or in the order in which they are presented.

[0115] With reference to block 302, in some embodiments, method 300 includes (A) obtaining a device including a rotating axis and a mixing chamber with a curved side that is not coaxial with the rotating axis. The mixing chamber shall be configured with any suitable shapes and / or sizes and in any suitable positions in the device (e.g., the disc or cartridge), provided there is a curved side that is not coaxial with the rotating axis. The device may be used for any suitable applications, including, but not limited to, mixing blood with buffer.

[0116] For example, as a non-limiting example, FIG. 4A illustrates a device 400-1 that rotates about a rotation axis 402-1 and includes a camera 410-1. The camera 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 illustrates a device 400-2 that rotates about a rotation axis 402-2 and includes a camera 410-2. The camera 410-2 has a curved side 420-2 that is not coaxial with the rotation axis 402-2. As yet another non-limiting example, FIG. 4C illustrates a device 400-3 that rotates about a rotation axis 402-3 and includes a camera 410-3. The 410-3 camera has a curved side 420-3 that does not Petition 870250101783, dated 06 / 11 / 2025, p. 31 / 110 28 / 67 is coaxial with the rotation axis 402-3. As yet another non-limiting example, FIG. 4D illustrates a device 400-4 that rotates about a rotation axis 402-4 and includes a camera 410-4. The camera 410-4 has a curved side 420-4 that is not coaxial with the rotation axis 402-4.

[0117] The mixing chamber contains a fluid 404 including 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 mixing chamber. However, the present disclosure is not limited to this. For example, in some embodiments, the volume of the fluid may be greater than 70% of the mixing chamber. In some embodiments, the fluid may have a volume that is 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 fluid may have a volume that is at most 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.

[0118] In some embodiments, the mixing chamber has an inflection point or inflection portion, such as inflection point / portion 430-1, 430-2, 430-3 and 430-4, at which the curvature of the mixing chamber changes sign. In some embodiments, the inflection point / portion is configured to prevent fluid from flowing into an inlet of the mixing chamber. In some embodiments, the curved side of the mixing chamber has a circular size of about 1 mm to about 10 mm, about 10 mm to about 20 mm, about 20 mm to about 30 mm or greater.

[0119] With reference to block 304, in some embodiments, method 300 includes (B) accelerating the device to a first velocity in a direction toward the curved side of the mixing chamber. The first velocity 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 specific implementations, the first velocity may be about 300 Petition 870250101783, dated 06 / 11 / 2025, p. 32 / 110 29 / 67 rpm at approximately 500 rpm, approximately 500 rpm at 700 rpm, or approximately 700 rpm at approximately 1000 rpm. However, the present disclosure is not limited to this. For example, in some specific implementations, first gear may be below 300 rpm or above 1000 rpm.

[0120] With reference to block 306, in some embodiments, method 300 includes (C) abruptly decelerating the device so that the fluid moves toward the curved side of the mixing chamber due to inertia. As the fluid moves toward it, the curved side of the mixing chamber translates the fluid motion into a circular motion that produces vortices, thus promoting the mixing of the two or more different components in the fluid. In some embodiments, the deceleration (C) causes the device to stop completely. 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 higher. However, the present disclosure is not limited to it.For example, in some modes, deceleration (C) can be performed at a speed of less than 500 rpm / s.

[0121] With reference 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 sufficient 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.

[0122] The method of the present disclosure utilizes the curvature of the mixing chamber and inertial motion to create vortices. This vortex motion generates shear forces, which can induce mixing of the fluids. This method is based on the principle that components with different Petition 870250101783, dated 06 / 11 / 2025, page 33 / 110 30 / 67 densities or viscosities or particles in the fluid will respond differently to the same inertial force, leading to relative movement between them and ultimately resulting in mixing. The device and method of the present disclosure can reduce hemolysis and coagulation and improve mixing efficiency. It is simple in design and does not require new features to be designed / added or the use of different disc materials / surface coatings.

[0123] Inertia-Based Device and Method for Directing Fluid.

[0124] Many factors play a role in the movement or direction of fluids in microfluidics. In microfluidic channels, capillary forces can dominate centrifugal forces, which can lead to non-uniform flow patterns or flow stagnation. This can result in incomplete distribution, uneven sample distribution, and blockages in the channels. At high rotational speeds, fluid viscosity can also affect flow behavior, leading to the formation of secondary flows and vortices that can interfere with desired flow patterns. Furthermore, certain types of ingredients, such as detergents dissolved in buffers, alter surface tension or other parameters and are thus prone to bubble formation. This may not be compatible with some centrifugal microfluidic systems and may limit the types of tests that can be performed using this technology.

[0125] To address these challenges, several techniques have been developed, such as optimizing channel design and surface coatings to control capillary forces, and selecting appropriate fluids with suitable viscosities and surface tensions. Furthermore, advanced and expensive microfluidic systems with active feedback and control mechanisms can be used to regulate flow patterns and ensure accurate results. Examples of such techniques or studies include those published in “Frequency-dependent transversal flow control in centrifugal microfluidics,” Lab Petition 870250101783, dated 06 / 11 / 2025, page 34 / 110 31 / 67 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 content of each is incorporated herein by reference in its entirety and for all purposes. They require complex systems to move or direct the fluid.

[0126] This disclosure addresses these and other needs in the art by developing a technique for directing liquid flow in centrifugal microfluidics using the inertial force of the liquid after sudden deceleration and interruption of the disc's rotation. This technique involves a chamber and an adjacent chamber, with a wide channel connecting the two, to transfer liquid from one chamber to the other. When the disc experiences a rapid reduction in rotational speed, the liquid responds by continuing to move in the direction tangent to the disc's rotational velocity vector. By carefully designing the size of the wide channel and taking into account factors such as air displacement and surface tension forces, it is possible to direct the liquid to the target chamber without the need for an external power source or additional complexity to the system.

[0127] With reference to FIG. 5, a flowchart is shown illustrating an exemplary method 500 for directing a fluid according to some embodiments of the present disclosure. In the flowchart, preferred parts of the method are shown in solid line boxes, while additional, optional or alternative parts of the method are shown in dashed line boxes. It should be noted that the processes disclosed in this document and exemplified in the flowchart may be, but do not have to be, performed in their entirety or in the order in which they are presented.

[0128] With reference to block 502, in some embodiments, method 500 includes (A) obtaining a device having an axis of rotation and a chamber having a path that is not coaxial with the axis of rotation, wherein the chamber contains a fluid. For example, as a non-limiting example, FIG. 6 illustrates Petition 870250101783, dated 06 / 11 / 2025, p. 35 / 110 32 / 67 a device 600 that is rotatable about an axis of rotation 602 and includes a chamber 610. The chamber 610 includes a path 620, for example, a channel that connects the chamber 610 to a downstream chamber. The chamber 610 contains a fluid 604. In some embodiments, the chamber 610 includes a barrier 630 that the fluid has to pass through to enter the downstream chamber.

[0129] With reference to block 504 and block 506, in some embodiments, method 500 includes (B) accelerating the device in a direction toward the chamber path and (C) abruptly decelerating the device so that the fluid moves toward the chamber path due to inertia. In some embodiments, acceleration (B) may bring the speed to 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 speed 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 higher. In some embodiments, deceleration (C) causes the device to stop completely. FIG. 6 shows that a considerable volume of fluid is transferred to the downstream chamber.

[0130] Although FIG. 6 illustrates chamber 610 as a mixing chamber, it should be noted that this is by way of example and is not limiting. Method 500 and technique can be applied to any other type of chamber. Furthermore, the shapes, sizes and positions of chamber 610 and via 620 can be easily modified to suit other applications. In some embodiments, the via is configured to be wide enough to allow easy fluid movement.

[0131] In embodiments where chamber 610 is a mixing chamber, method 500 can be used to direct the fluid after fluid mixing. Fluid mixing can be performed using method 300 or by any other mixing techniques (e.g., using particles). Petition 870250101783, dated 06 / 11 / 2025, p. 36 / 110 33 / 67 magnetic). For example, referring again to FIG. 3 and FIG. 4C, in some embodiments, the mixing chamber 410-3 includes a path 440 (e.g., a channel) opposite the curved side 420-3 of the mixing chamber. The path 440 connects the mixing chamber 410-3 to a downstream chamber. In some embodiments, the mixing chamber 410-3 also includes a barrier 450 that the fluid has to pass through to enter the downstream chamber. In some of these embodiments, method 300 may include (E) slowly accelerating the device to a second speed in a direction toward the path and (F) abruptly decelerating the device so that the fluid moves toward the path of the mixing chamber due to inertia.

[0132] The use of inertia to direct flows has potential applications in various microfluidic processes, such as sample preparation and analysis, drug delivery, and microscale synthesis. There is no need for special surface coatings to control capillary forces, no need for advanced and expensive microfluidic systems with active feedback and control mechanisms to regulate flow patterns and ensure accurate results, and no need to select appropriate fluids with suitable viscosities and surface tensions. Parameters such as chamber curvature, barrier height, path length, width, and / or depth can be optimized to ensure reliable and reproducible results.

[0133] Channel Capable of Bubble-Free Priming.

[0134] In microfluidics, it is difficult to remove all air bubbles from the capillary before filling it with a sample. The presence of air bubbles can cause errors in sedimentation analysis, as it can alter the sedimentation rate of particles or interfere with the optical detection of the sedimentation process. One approach to achieving bubble-free preparation is to use a vacuum or pressure system to evacuate air from the capillary before filling it with the sample. However, this technique can be difficult to implement, particularly for small-diameter capillaries or samples. Petition 870250101783, dated 06 / 11 / 2025, p. 37 / 110 34 / 67 with low sedimentation rates. Another approach is to use a surfactant or wetting agent to help displace air and wet the inner surface of the capillary. However, the choice of surfactant and its concentration can affect the sedimentation rate, morphology, and integrity of soft biological objects such as blood cells, and thus introduce additional sources of error. The use of a step-through channel was proposed in “Single-Step Hematocrit Centrifuge Determination in a 10-$ Processing Device,” Biomed Microdevices (2007) 9:795799, the contents of which are incorporated herein by reference in their entirety and for all purposes. However, it uses hydrophilic surface treatment and relies on the capillary forces required to prepare the channel.Overall, obtaining a bubble-free preparation from a dead-end sedimentation capillary requires careful attention to the choice of material, method, equipment, and sample preparation, as well as optimization of experimental conditions to ensure accurate and reproducible sedimentation analysis.

[0135] The present disclosure addresses these and other needs in the art by providing a capillary channel where initiation with the liquid is based on the differentiation of flow resistances that propagate along different bands of the channel. As such, the capillary channel of the present disclosure can be made of any untreated material, including hydrophilic and hydrophobic, while still achieving bubble-free initiation.

[0136] With reference to FIGS. 7A and 7B, a device 700 is shown according to some embodiments of the present disclosure. The device 700 is rotatable about an axis of rotation 702. The device 700 includes a ventilation port 710 and a capillary channel 720 positioned radially outward from the ventilation port relative to the axis of rotation 702.

[0137] The 720 capillary channel is configured to have a step-shaped cross-section to facilitate bubble-free initiation. It is designed to transport fluid (e.g., blood) from the inlet to the blind capillary using fluid resistance differentiation driven by centrifugation. The distinct depth profile of the capillary reliably avoids the Petition 870250101783, dated 06 / 11 / 2025, page 38 / 110 35 / 67 air entrapment during the filling process.

[0138] The capillary channel 720 includes an open end 721 and a dead end 722 positioned radially outward from the open end relative to the axis of rotation. The capillary channel may be oriented along the radius or at an angle to it. 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 lane 730, a second lane 740, and a third lane 750. The first lane has an inlet at the open end to receive a fluid. The third lane has an outlet at the open end to vent air. For example, in some embodiments, the outlet of the third lane of the capillary channel is connected to the vent port. The second lane is formed between the first and third lanes and connected to the first and third lanes.The first, second, and third channels are configured so that the second channel has a different flow resistance than the first and third channels, thus allowing the fluid to flow first through the first channel 730, from the open end 721 to the blind end 722, and then flow through the second channel 740, the third channel 750, or both, from the blind end 722 to the open end 721, to facilitate bubble-free filling.

[0139] In some embodiments, the first, second, and third lanes collectively form a stepped cross-section perpendicular to a length direction of the capillary channel as illustrated in FIG. 7B. In some embodiments, the first and third lanes are deeper than the second lane, for example, the shallow second lane separating the deeper first and third lanes. The boundary extent acts as a barrier, creating a fluidic separation of the two levels at the adjacent edge. Filling of the dead-end channel is promoted at a level where the fluid is exposed to lower resistance, while air is removed through the higher resistance level as the fluid progresses downstream. As the fluid reaches the dead end of the capillary, it penetrates the adjacent level to fill the capillary in the reverse direction without trapping air bubbles. Petition 870250101783, dated 06 / 11 / 2025, p. 39 / 110 36 / 67

[0140] The third lane has access to the vent and is added for additional reliability to extend the application range, especially if the fluid (e.g., blood) crosses the edge separating lanes 1 and 2 before reaching the dead end. This can happen if there are defects in the wall or if the resistance difference is insufficient for a clear separation of the flows. This process ensures that the capillary is filled without air bubbles. The number of lanes does not need to be three. For example, the number of lanes could be two, or it could be more than three, with the last one having access to the vent.

[0141] The first and third lanes may be configured substantially the same to each other (e.g., have the same width and depth) or differently from each other (e.g., have different widths and / or depths). In some embodiments, at least two of the first, second, and third lanes have the same width. In some embodiments, at least two of the first, second, and third lanes have different widths. In some specific implementations, the first and third lanes may have a depth of approximately 500 pm to 1,000 pm, approximately 1,000 pm to 1,500 pm, or approximately 1,500 pm to 2,000 pm. The second lane may be approximately 200 pm to approximately 500 pm, approximately 300 pm to approximately 700 pm, or approximately 600 pm to 1,000 pm shallower than the first and / or third lane. The radial length of the capillary canal can 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 lane can be chosen so that the resistance to flow is different between shallow and deep lanes. In some embodiments, the width of the first, second, and / or third lane may be in the range of about 100 pm to about 500 pm, about 300 pm to about 700 pm, or about 500 pm to 1000 pm. However, the present disclosure is not limited to this. Depending on the applications, the channel, including the first, second, and third lanes, may have any other appropriate shapes and sizes. Petition 870250101783, dated 06 / 11 / 2025, p. 40 / 110 37 / 67

[0142] The capillary channel of the present disclosure does not require a vacuum or pressure system to evacuate air from the capillary before filling it with a sample, or surfactant or wetting agent to help displace air and wet the inner surface of the capillary. It is simple and can be used for various applications.

[0143] Compressed structure to direct the fluid.

[0144] Surface tension is a critical factor in microfluidics, where the behavior of liquids can be significantly different from their bulk counterparts due to the small scales involved. The interaction between the liquid and the channel walls can lead to various phenomena, including capillary flow, where the liquid follows the shape of the channel edge rather than the direction of the applied force. In some cases, this can be undesirable and needs to be eliminated. For example, surface tension can influence the direction a liquid follows after exiting a channel expansion in a microfluidic, creating a meniscus or curved surface at the liquid-air interface. The shape and strength of the meniscus depend on the fluid properties, such as its surface tension, as well as the shape and properties of the channel surface.If the surface tension of the liquid is high and the channel extension shape has an edge with corners that promote wetting, the liquid will tend to spread and follow the direction along the edge instead of the centrifugal force. This is known as capillary flow.

[0145] When fluid leaves a small microfluidic channel and enters a larger chamber, a surface interaction problem can arise. The surface properties of the larger chamber at the junction can influence flow behavior, directing it in an uncontrolled direction. For example, if the surface has non-uniform physical and chemical properties, the liquid may not leave the fitting in the direction of centrifugal force, but follow the angle of the fitting, which can affect the operation of the system.

[0146] These technical problems can be mitigated through the use of surface treatment or the addition of surfactants. However, they add Petition 870250101783, dated 06 / 11 / 2025, p. 41 / 110 38 / 67 plus manufacturing cost, can potentially cause cell damage and are complex. The present disclosure addresses these and / or other issues in the art by providing an extension so that the centrifugal force acts in the opposite direction to the capillary force vector and thus compensates for it.

[0147] With reference to FIGS. 8A-8C, a device 800 is shown according to some embodiments of the present disclosure. The device 800 is rotatable about an axis of rotation 802. The device 800 includes a chamber 810 and a channel 820 connected to the chamber to distribute a fluid 804 to the chamber. The chamber and channel collectively form a junction 830 that minimizes or eliminates capillary flow when the fluid exits the channel (e.g., a channel outlet) into the chamber. In some embodiments, the junction allows the fluid to flow from the channel outlet into the chamber in a centrifugal force direction.

[0148] In some embodiments, the channel includes a protruding portion 840 that forms at least part of the junction. The protruding portion 840 is configured so that the fluid is compressed in the protruding part for a time until the centrifugal force exceeds the surface tension forces that retain the fluid. During this retention moment, there is no movement of the fluid to the left or to the right, as would be the case with the straight-line edges shown in FIGS. 8D and 8E, where flat walls allow the fluid (e.g., blood) 804 to flow unpredictably. As soon as the centrifugal force overcomes the surface tension, the interaction of the fluid with the surface 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.

[0149] The protruding portion can be configured with any appropriate shapes and sizes. As a non-limiting example, FIG. 8B illustrates that the protruding portion includes a U-shaped wall 841 on each side of the channel at the channel outlet. As another non-limiting example, FIG. 8C illustrates that the protruding portion includes a V-shaped wall 842 on each side of the channel at the channel outlet. In some embodiments, the wall 811 of chamber 810 Petition 870250101783, dated 06 / 11 / 2025, p. 42 / 110 39 / 67 adjacent to the channel outlet is curved radially inward relative to the channel outlet to form at least a portion of the junction. By applying a centrifugal force that exceeds the surface tension forces, the fluid can be forced to move in a desired direction. This is achieved by compressing the fluid along the channel length, creating a balancing moment between the forces, and then releasing it when the centrifugal force becomes dominant.

[0150] In some specific implementations, the channel may have a width of 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 may have a depth of 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 radii of curvature of the U-shaped walls can be from about 100 μm to about 200 μm, from about 200 μm to about 300 μm, from about 300 μm to about 400 μm, or from about 400 μm to about 500 μm. However, the present disclosure is not limited to this. Depending on the applications, the channel and the protruding portion can be configured with various shapes and sizes.

[0151] The compressed structure of the present disclosure negates the use of surface treatments that would add further manufacturing costs and potentially cause damage to cells. The compressed structure of the present disclosure also negates the need to add surfactants that would be complex and potentially cause damage to cells.

[0152] Device and Method for Measuring Depths with Self-Calibration Capability.

[0153] There can be several causes of 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 inadequate control of temperature, pressure, cooling rate, humidity, etc. To account for these variabilities in the depths of molded consumables, an appropriate measurement technique is required. Petition 870250101783, dated 06 / 11 / 2025, page 43 / 110 40 / 67 should be used. Examples of techniques include profilometers, depth gauges, laser scanners, optical interferometry, and ultrasonic sensors. However, measuring each consumable depth during its assembly is a laborious and time-consuming procedure. Furthermore, a consumable's depth may change as it ages.

[0154] The uneven depth of some consumable compartments can cause unstable operation. For example, if the depth of the molded measuring chamber in a microfluidic consumable is altered, this can result in a mismatch in the volume of liquid dispensed, which can lead to incorrect test results. Microfluidic consumables are used for precise measurements and handling of small quantities of fluids in applications such as medical diagnostics, drug discovery, and genetic analysis. Inaccurate measurement due to variations in the depth of molded measuring chambers can result in incorrect measurements, leading to false-positive or false-negative results, which can have serious consequences in critical applications. Therefore, it is important that the depth of the molded compartments in microfluidic consumables is measured accurately to ensure correct and reliable test results.

[0155] This disclosure addresses these and / or other issues in the art by implementing self-calibration features that can be used to measure production deviations in the depth of devices (e.g., molded consumables) directly at the user's location and / or as part of an analysis method. The measurement is fast (e.g., within seconds) and without any labor involvement.

[0156] With reference to FIG. 9, a flowchart is shown illustrating an exemplary method 900 for measuring depths despite manufacturing variabilities according to some embodiments of the present disclosure. In the flowchart, preferred parts of the method are shown in solid-line boxes, while additional, optional or alternative parts of the method are shown in dashed-line boxes. It should be Petition 870250101783, dated 06 / 11 / 2025, page 44 / 110 41 / 67 Note that the processes disclosed in this document and exemplified in the flowchart can be, but do not need to be, executed in their entirety or in the order in which they are presented.

[0157] With reference to block 902, in some embodiments, method 900 includes (A) obtaining a device including 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known. For example, as a non-limiting example, FIGS. 10A and 10B illustrate a device 1000 including a structure 1010. The 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 and second depths are different from each other. These depths are not necessarily equal to their nominal values, as they are subject to manufacturing variations.However, the difference between these depths may correspond to the nominal depth difference because, in many cases, production variability has a similar effect on variance. In other words, although the first and second depths may not be their nominal values, the nominal depth difference (delta L) between the first and second depths is known. In some embodiments, once the device is obtained, an absorbent dye is filled into the structure.

[0158] With reference to block 904, in some embodiments, method 900 includes (B) measuring a first optical density (OD1) of the absorbing dye in the first portion of the structure and a second optical density (OD2) of the absorbing dye in the second portion of the structure. In some embodiments, the first and second optical densities are measured using a spectrophotometer or a microfluidic device that measures absorbance.

[0159] With reference to block 906, in some modalities, the Petition 870250101783, dated 06 / 11 / 2025, p. 45 / 110 42 / 67 method 900 includes (C) calculating an optical density difference (delta OD) between the first and second optical densities.

[0160] With reference to block 908, in some embodiments, method 900 includes (D) calculating a ratio of the optical density difference to the nominal depth difference, where the ratio represents a product of an extinction coefficient and a concentration of the absorbing dye. For example, according to Beer-Lambert's law: ODi = ecL1 (1) OD2 = ecL2 (2) where e is the extinction coefficient of the absorbing dye, c is its concentration, L1 and L2 are the depths of the first and second depths. It is not necessary to know the concentrations and the extinction coefficient of the dye.

[0161] In some modalities, the ratio is calculated as follows: ec = delta OD / delta L (3)

[0162] With reference to block 910, in some embodiments, method 900 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, a depth of any additional structure of the device, or any combination thereof. For example, in some embodiments, the ratio obtained (ec) is then plugged back into equation (1) to calculate the first depth L1 and / or equation (2) to calculate the second depth L2.

[0163] While FIG. 10A illustrates the device with a 1010 structure and FIG. 10B illustrates the 1010 structure with two different depths, it should be noted that the device may have more than 1, more than 2, more than 3, more than 4, more than 5 or more than 10 structures, and a structure may have more than 2, more than 3, more than 4 or more than 5 different portions with different depths. The structures may be positioned in any locations. Petition 870250101783, dated 06 / 11 / 2025, page 46 / 110 43 / 67 suitable on the device to allow multiple measurements to ensure consistency in depth. The structures can be configured the same as each other or differently from each other. They can also have different pairs of levels to calibrate deep and shallow channels, and can be two or more connected in series or independent channels.

[0164] For example, in some embodiments, the 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 and second depths are different from each other, but a nominal depth difference between the first and second depths is known. This allows for the self-calibration of the depth of any structure (e.g., one or more structures or other structures) of the device independently of variations in the manufacture of the device. In some embodiments, one or more structures include a first structure and a second structure at different locations in the device. In some of these embodiments, the nominal depth difference of the first structure is the same as that of the second structure.Alternatively, in some configurations, the nominal depth difference of the first structure is different from that of the second structure.

[0165] Device and Method for Measuring Concentration Despite Manufacturing Variability.

[0166] Measuring hemoglobin concentration is a critical test for diagnosing anemia, monitoring blood loss, and assessing overall health. The use of microfluidic technology has made it possible to perform this test with a small sample size and in a short period of time. However, there may be variability in the manufacturing of microfluidic consumables, which can affect the accuracy of test results. There may be several causes of manufacturing variability in the depth of molded consumables. Some of these are inconsistent molding conditions, where the depth of the consumables Petition 870250101783, dated 06 / 11 / 2025, page 47 / 110 44 / 67 molded can be affected by inadequate control of temperature, pressure, cooling rate, humidity and / or other factors.

[0167] One way to solve this problem is to calibrate the microfluidic device before use. Calibration involves determining the sensitivity and accuracy of the device by measuring the hemoglobin concentration of a standard solution. This information can then be used to adjust the test results obtained from the device. However, this calibration depends on the consistency of consumable manufacturing. For example, if the concentration determination is based on the measurement of the optical density of hemoglobin, then the optical pathway is a critical parameter. In this respect, the depth of the microfluidic optical compartment must be accurately determined.

[0168] This disclosure addresses these and / or other issues in the art by providing a device and method for determining hemoglobin concentration by measuring its optical density without the need for absolute depth determination. The methodology of this approach is similar to the methodology for measuring manufacturing variabilities.

[0169] With reference to FIG. 11, a flowchart is shown illustrating an exemplary method 1100 for measuring concentration despite manufacturing variability according to some embodiments of the present disclosure. In the flowchart, preferred parts of the method are shown in solid-line boxes, while additional, optional or alternative parts of the method are shown in dashed-line boxes. It should be noted that the processes disclosed in this document and exemplified in the flowchart may be, but do not have to be, performed in their entirety or in the order in which they are presented.

[0170] With reference to block 1102, in some embodiments, method 1100 includes (A) obtaining a device including a structure located in a path 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 and the Petition 870250101783, dated 06 / 11 / 2025, p. 48 / 110 45 / 67 second depths are different from each other, but the nominal depth difference between the first and second depths is known. For example, as a non-limiting example, FIGS. 12A and 12B illustrate a device 1200 including a structure 1210 located in a path 1220 of a mixture having a first component (e.g., a mixture containing hemoglobin). The 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 and second depths are different from each other. These depths are not necessarily equal to their nominal values, as they are subject to manufacturing variations. However, the difference between these depths may correspond to the nominal depth difference because, in many cases, production variability has a similar effect on the variance.In other words, although the first and second depths may not be their nominal values, the difference in nominal depth (delta L) between the first and second depths is known.

[0171] With reference to block 1104, in some embodiments, method 1100 includes (B) measuring a first optical density (ODi) of the first component in the first portion of the structure and a second optical density (OD2) of the first component in the second portion of the structure. In some embodiments, the first and second optical densities are measured using a spectrophotometer or a microfluidic device that measures absorbance.

[0172] With reference to block 1106, in some embodiments, method 1100 includes (C) calculating an optical density difference (delta OD) between the first and second optical densities.

[0173] With reference to block 1108, in some embodiments, method 1100 includes (D) determining a concentration of the 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), delta OD is a function of delta L as follows: Petition 870250101783, dated 06 / 11 / 2025, p. 49 / 110 46 / 67 delta OD = ec delta L (4)

[0174] As such, the optical density difference (delta OD) obtained from calculation (C) can be compared with a calibration curve that was constructed for the same optical path as delta L. The calibration curve can be created using a high-precision depth quartz cuvette. The output signal can thus be used to determine the concentration of the first component (e.g., hemoglobin concentration) in the mixture. It is not necessary to know the extinction coefficient of the first component (e.g., hemoglobin), as it uses the calibration curve.

[0175] In some embodiments, if the extinction coefficient for the first component is known (for example, the extinction coefficient is determined for the wavelength used in the optical system of the device), then the calibration curve will not be necessary. 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, because delta OD, delta L and e are known.

[0176] With reference to blocks 1110 to 1116, in some embodiments, method 1100 includes (E) creating, prior to determination (D), the calibration curve. In some embodiments, creation (E) includes (i) preparing a series of standard solutions with 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 in one or more optical pathways, thereby obtaining 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 pathways.

[0177] For example, in some embodiments where the first component is hemoglobin, the method includes the preparation of a series of standard solutions with known concentrations of hemoglobin, using a Petition 870250101783, dated 06 / 11 / 2025, p. 50 / 110 47 / 67 A spectrophotometer or a microfluidic device is used to measure the absorbance of each of the standard solutions at specific wavelength(s) for hemoglobin, plotting the absorbance values ​​against the corresponding hemoglobin concentrations to create a calibration curve. In some embodiments, the method also includes measuring the absorbance of the 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.

[0178] Like the 1000 device, the 1200 device can have more than one 1210 structure. Similarly, like the 1010 structure, the 1210 structure can have more than two different portions. Furthermore, a device can have both the 1010 structure(s) and the 1210 structure(s) to perform both the 1000 method and the 1200 method.

[0179] The device and method of the present invention make absorbance, and therefore concentration measurement, less dependent on depth and thus improve measurement accuracy.

[0180] With reference to FIG. 13, a device 1300 (for example, a disk) is shown according to some exemplary embodiments of the present disclosure. The device 1300 rotates around a rotation axis, as does the vertical rotation axis 1303. In some implementations, the device 1300 can be rotated, during one or more processes, at a speed of at least about 1000 rpm, at least about 1200 rpm, at least about 1400 rpm, at least about 1600 rpm, at least about 1800 rpm, at least about 2000 rpm, at least about 2200 rpm, at least about 2400 rpm, at least about 2600 rpm, at least about 2800 rpm, at least about 2900 rpm, at least about 3000 rpm, at least about 3500 rpm, at least about 4000 rpm, at least about 4500 rpm, at least about 5000 rpm, at least less approximately 5500 rpm, at least approximately 6000 rpm, at least approximately 6500 rpm, or at least Petition 870250101783, dated 06 / 11 / 2025, p. 51 / 110 48 / 67 minus about 7000 rpm. In some implementations, the 1300 device can be rotated, during one or more processes, at a speed of at most about 500 rpm, at most about 600 rpm, at most about 700 rpm, at most about 800 rpm, at most about 900 rpm, at most about 1000 rpm, at most about 1200 rpm, at most about 1400 rpm, at most about 1600 rpm, at most about 1800 rpm, at most about 2000 rpm, at most about 2200 rpm, at most about 2400 rpm, at most about 2600 rpm, at most about 2800 rpm, at most about 2900 rpm, at most about 3000 rpm, at most about 3500 rpm, at most about 4000 rpm, at most about 4500 rpm, or at most at around 5000 rpm.

[0181] In some embodiments, the 1300 device (e.g., the disk) includes a plurality of units, such as units 1310-1, 13102, 1310-3, arranged circumferentially. In some embodiments, the 1300 device includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 units. In some embodiments, a 1310 unit includes one or more features / components / devices (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) disclosed in this document. In some embodiments, each 1310 unit includes one or more features / components / devices disclosed in this document. In some embodiments, at least one unit is identical to another unit in the plurality of units.In some forms, at least one unit is different from the other units in the plurality of units.

[0182] With reference to FIG. 14, a device 1400 (for example, a disk) is shown according to some exemplary embodiments of the present disclosure. The device 1400 is rotatable about an axis of rotation, as is the vertical axis of rotation 1403. In some implementations, the device 1400 can be rotated, during one or more processes, at a Petition 870250101783, dated 06 / 11 / 2025, p. 52 / 110 49 / 67 speed of at least about 1000 rpm, at least about 1200 rpm, at least about 1400 rpm, at least about 1600 rpm, at least about 1800 rpm, at least about 2000 rpm, at least about 2200 rpm, at least about 2400 rpm, at least about 2600 rpm, at least about 2800 rpm, at least about 2900 rpm, at least about 3000 rpm, at least about 3500 rpm, at least about 4000 rpm, at least about 4500 rpm, at least about 5000 rpm, at least about 5500 rpm, at least about 6000 rpm, at least about 6500 rpm or at least about 7000 rpm.In some implementations, the 1400 device can be rotated, during one or more processes, at a speed of at most about 500 rpm, at most about 600 rpm, at most about 700 rpm, at most about 800 rpm, at most about 900 rpm, at most about 1000 rpm, at most about 1200 rpm, at most about 1400 rpm, at most about 1600 rpm, at most about 1800 rpm, at most about 2000 rpm, at most about 2200 rpm, at most about 2400 rpm, at most about 2600 rpm, at most about 2800 rpm, at most about 2900 rpm, at most about 3000 rpm, at most about 3500 rpm, at most about 4000 rpm, at most about 4500 rpm, or at most at around 5000 rpm.

[0183] In some embodiments, the 1400 device (e.g., the disk) includes a plurality of units, such as units 1410-1, 14102, 1410-3, arranged circumferentially. In some embodiments, the 1400 device includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more than 10 units. In some embodiments, a 1410 unit includes one or more features / components / devices (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) disclosed in this document. In some configurations, each 1410 unit includes one or more features / components / devices disclosed in this document. Petition 870250101783, dated 06 / 11 / 2025, page 53 / 110 In 50 / 67 modalities, at least one unit is identical to another unit in the plurality of units. In some modalities, at least one unit is different from the other units in the plurality of units.

[0184] Exemplary workflows.

[0185] With reference to FIG. 15, an exemplary workflow 1500 is illustrated according to some exemplary embodiments of this disclosure. Workflow 1500 can be performed on any suitable devices disclosed in this document (e.g., device 1300 or device 1400). Workflow 1500 can also be automated. Furthermore, although specific samples (e.g., whole blood) are used in the workflow description, it should be noted that this disclosure is not limited to them. Other samples, such as those disclosed in this document, may be used. In addition, the processes disclosed in this document and exemplified in workflow 1500 can be, but do not have to be, performed in their entirety or in the order in which they are presented.

[0186] The 1500 workflow can be configured to perform one or more assays, including, but not limited to, white blood cell (WBC) assay, red blood cell (RBC) assay, and / or hemoglobin (HgB) assay. In some embodiments, the 1500 workflow can be configured to perform a plurality of assays, for example, any two or all of the WBC assay, RBC assay, and hemoglobin assay. In some embodiments, the 1500 workflow can be configured to perform one or more additional or optional processes, such as an autocalibration process.

[0187] In some embodiments, workflow 1500 includes a process 1502 that charges a buffer (e.g., water) to a device (e.g., device 1400). The buffer charging can be performed when the device is stationary or rotating at a low speed. In embodiments where multiple tests must be performed, the buffer can be Petition 870250101783, dated 06 / 11 / 2025, page 54 / 110 51 / 67 loaded for all tests that must be performed. As a non-limiting example, FIG. 16A-1 (a schematic diagram) and FIG. 16A-2 (a photograph) illustrate the loading of a buffer for device 1400.

[0188] In some embodiments, workflow 1500 includes a process 1504 that loads a sample (e.g., blood) into the device. Sample loading can be performed when the device is stationary or rotating at a low speed. Furthermore, sample loading can be performed before, concurrently with, or subsequently to 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. 16B1 (a schematic diagram) and FIG. 16B-2 (a photograph) illustrate the loading of a sample (e.g., blood) into the device 1400. In some embodiments, the sample is loaded into the device, passing through the trapping channels step by step (e.g., the device / structure 200 disclosed in this document) for all assays.

[0189] In some embodiments, workflow 1500 includes a process 1506 that overflows the buffer. In this process, the device (e.g., device 1400) is rotating and, in some cases, at a predefined speed profile. In embodiments where multiple tests are to be performed, buffer overflow can be performed simultaneously for all tests (e.g., measurement occurs at approximately the same time for all tests). As a non-limiting example, FIG. 16C-1 (a schematic diagram) and FIG. 16C-2 (a photograph) illustrate buffer overflow according to the design of device 1400.

[0190] In some embodiments, workflow 1500 includes a process 1508 that overflows the sample (e.g., blood). In this process, the device (e.g., device 1400) is rotating and, in some cases, at a predefined speed profile. In some embodiments, the sample is drained or overflowed into a hematocrit column, such as Petition 870250101783, dated 06 / 11 / 2025, page 55 / 110 52 / 67 a step-by-step channel without bubbles (e.g., device 700 disclosed in this document). In embodiments where multiple tests are to be performed, sample overflow can be performed simultaneously for all tests (e.g., measurement occurs at approximately the same time for all tests). As a non-limiting example, FIG. 16D-1 (a schematic diagram) and FIG. 16D-2 (a photograph) illustrate sample overflow according to the design of device 1400.

[0191] In some embodiments, workflow 1500 includes a process 1510 that measures the sample (e.g., blood). In this process, the device (e.g., device 1400) is rotating and, in some cases, at a predefined speed profile. In some embodiments, during this process, a valve (e.g., device / structure 100) is broken. The sample is directed to a mixing chamber (e.g., device / structure 400 or device / structure 600) through a compressed channel (e.g., device / structure 800). In embodiments where multiple assays must be performed, sample measurement can be performed simultaneously for all assays (e.g., measurement occurs at approximately the same time for all assays). As a non-limiting example, FIG. 16E-1 (a schematic diagram) and FIG. Figure 16E-2 (a photograph) illustrates the sample measurement according to the 1400 device design.

[0192] In some embodiments, workflow 1500 includes a process 1512 that measures the buffer. In this process, the device (e.g., device 1400) is rotating and, in some cases, at a predefined speed profile. In some embodiments, during this process, a valve (e.g., device / structure 100) is broken. The buffer is directed to a mixing chamber (e.g., device / structure 400 or device / structure 600) through a compressed channel (e.g., device / structure 800). In embodiments where multiple tests must be performed, the buffer measurement can be performed simultaneously for Petition 870250101783, dated 06 / 11 / 2025, page 56 / 110 53 / 67 all tests (i.e., the measurement occurs at approximately the same time for all tests). In some embodiments, in this process, a sample chamber or chambers are also subjected to flash. As a non-limiting example, FIG. 16F-1 (a schematic diagram) and FIG. 16F2 (a photograph) illustrate the buffer measurement according to the 1400 device design.

[0193] In some embodiments, workflow 1500 includes a process 1514 that traps the remaining sample and / or overflows the sample (e.g., blood). In this process, the spinning is accelerated (e.g., the rotation speed of the device is increased). In some embodiments, the remaining sample, if any, is trapped. In some embodiments, the excess sample, if any, is overflowed to a hematocrit column. As a non-limiting example, FIG. 16G-1 (a schematic diagram) and FIG. 16G-2 (a photograph) illustrate the trapping of the remaining sample and / or the overflow of the sample according to the device design 1400.

[0194] In some embodiments, workflow 1500 includes a process 1516 that mixes the measured sample and the measured buffer. In some embodiments, mixing is achieved by alternately accelerating and decelerating the device's rotation speed (e.g., alternately increasing and decreasing the device's rotation speed). Increasing / decreasing the device's rotation speed (e.g., device 1400) can be repeated as desired, programmed, or until the solution is adequately / completely mixed. In some embodiments, increasing / decreasing the device's rotation speed can be repeated approximately 10 times, approximately 20 times, approximately 30 times, approximately 40 times, approximately 50 times, or approximately 60 times. In embodiments where multiple assays are to be performed, the solution volumes for different assays may be different.However, the devices (e.g., device 1400) disclosed in this document are configured so that the mixing efficiency is similar for all tests. This allows for mixing to be performed. Petition 870250101783, dated 06 / 11 / 2025, page 57 / 110 54 / 67 for all tests simultaneously (i.e., approximately at the same time and / or approximately the same number of cycles for all tests).

[0195] In some embodiments, mixing is conducted using an inertial motion principle, for example, by increasing the rotational speed of the device to a threshold speed and then suddenly stopping the spinning (e.g., by decreasing the rotational speed to a low or zero level), as disclosed in this document in relation to device / structure 400 and device / structure 600, thus pushing the liquid to one side. This movement is all in one direction. This not only mixes the buffer with the sample but also dissolves the respective lyophilized reagents (e.g., lyo-spheres) in the chambers. As a non-limiting example, FIG. 16H-1 (a schematic diagram) and FIG. 16H-2 (a photograph) illustrate the mixing of the measured sample and the measured buffer according to the design of device 1400.

[0196] In some embodiments, the mixing process dissolves the lyophilized bead in a mixing chamber configured for a WBC assay. The dissolved lyophilized bead causes the RBC to lyse and / or stain the platelets for fluorescence imaging when desired. In some embodiments, the sample or solution becomes translucent. In some embodiments, the WBCs are also labeled for fluorescence imaging. In some embodiments, the mixing process dissolves the lyophilized bead in a mixing chamber configured for an RBC assay. In some embodiments, the dissolved lyophilized bead stains the platelets for fluorescence imaging when desired. In some embodiments, the mixing process dissolves the lyophilized bead in a mixing chamber configured for a HgB assay.In some modalities, the dissolved lyophilized granule lyses all cells to obtain a homogeneous translucent mixture for hemoglobin absorbance measurement, for example, by imaging and / or other methods. Petition 870250101783, dated 06 / 11 / 2025, page 58 / 110 55 / 67

[0197] In some embodiments, the workflow 1500 includes a process 1518 that distributes the mixture (e.g., the solution after the mixing process) to one or more detection channels (e.g., the device / structure 1200) for measurement. In some embodiments, the mixture is distributed to its respective imaging channels by accelerating the device wiring in the opposite direction (e.g., in a direction opposite to that used for mixing) at a threshold speed, then stopping abruptly 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 (a schematic diagram) and FIG. 16I-2 (a photograph) illustrate the distribution of the mixture to one or more detection channels according to the device design 1400.

[0198] In some embodiments, workflow 1500 includes a process 1520 that measures the optical density (OD) of HgB. In some embodiments, the measurement of the optical density (OD) of HgB is conducted using a method disclosed in this document or similar methods. In some embodiments, a detection channel is a step-through optical channel (e.g., device / structure 1200). As a non-limiting example, FIG. 16I-1 (a schematic diagram) and FIG. 16I-2 (a photograph) illustrate the OD measurement of HgB according to the device design 1400.

[0199] The 1500 workflow may include one or more additional, optional, or alternative processes. For example, in some embodiments, the 1500 workflow includes a process that allows a WBC assay (e.g., to measure the number of white blood cells in the blood sample). In some implementations, the 1500 workflow includes an additional or optional process that allows cells to settle within one or more imaging channels that are configured for a WBC assay, as illustrated in FIG. 16J-1 (a schematic diagram) and FIG. 16J-2 (a photograph). After the cells are settled in the imaging channels Petition 870250101783, dated 06 / 11 / 2025, p. 59 / 110 56 / 67 image, each of the one or more image generation channels generates an image and / or the image is analyzed for the WBC assay (e.g., WBC count).

[0200] In some embodiments, the 1500 workflow includes a process that enables an RBC assay (e.g., to measure the number of erythrocytes in the blood sample). For example, in some implementations, the 1500 workflow includes an additional or optional process that allows cells to settle within one or more imaging channels that are configured for an RBC assay, as illustrated in FIG. 16K-1 (a schematic diagram) and FIG. 16K-2 (a photograph). After the cells are settled in the imaging channels, each of the one or more imaging channels generates an image and / or the image is analyzed for the RBC assay.

[0201] In some embodiments, the 1500 workflow includes a process that allows for hematocrit measurement (e.g., measuring the hematocrit level or the proportion of red blood cells in the blood sample). For example, in some implementations, the 1500 workflow includes an additional or optional process that separates plasma from the blood sample. Plasma can be separated from the blood sample (e.g., the blood sample from sample overflow) by rotating the device at high speed after all other assays have been performed (e.g., detection channels for all other assays are photographed), as illustrated in FIG. 16L-1 (a schematic diagram) and FIG. 16L-2 (a photograph).

[0202] In some embodiments, workflow 1500 includes a process that allows for self-calibration. Self-calibration can be performed according to method 900 and / or device / structure 1000 disclosed in this document. As a non-limiting example, FIG. 16M-1 (a schematic diagram), FIG. 16M-2 (a photograph), and FIG. 16M-3 (a photograph) illustrate self-calibration according to the design of device 1400, which includes one or more devices / structures 1000 or a structure similar to Petition 870250101783, dated 06 / 11 / 2025, pp. 60 / 110 57 / 67 device / structure 1000.

[0203] The devices and methods disclosed in this document may be used in a variety of applications, including, but not limited to, clinical chemistry, immunoassays, and hematology. Examples of clinical chemistry, immunoassays, and / or hematology are disclosed in WO2018 / 119437, WO2018 / 140719, WO2022 / 029731, and WO 2022 / 029732, the contents of each application being incorporated herein by reference in their entirety. The devices and methods disclosed in this document may be operated or performed by a system similar to those disclosed in U.S. Patent Application No. 17 / 371,746, the contents of which are incorporated herein by reference in their entirety.

[0204] Illustration of the technology in question as clauses.

[0205] Several examples of aspects of the disclosure are described as numbered clauses (1, 2, 3, etc.) for convenience. These are provided as examples and do not limit the technology in question.

[0206] 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 a flow direction that is the same as or smaller than the upstream chamber, thus 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 the first outlet of the first channel, thus forming a hydrophilic junction at the first outlet of the first channel.

[0207] Clause 2. The valve of Clause 1, further comprising: a second channel 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.

[0208] Clause 3. The valve of Clause 2, wherein the second channel has a cross-section perpendicular to the flow direction the same as the Petition 870250101783, dated 06 / 11 / 2025, pp. 61 / 110 58 / 67 first channel.

[0209] Clause 4. The valve of Clause 2, where the second channel has a cross-section perpendicular to the flow direction different from the first channel.

[0210] Clause 5. The valve of any of Clauses 2 to 4, where the second channel is longer than the first channel.

[0211] Clause 6. The valve, according to any of the preceding Clauses, in which the compartment is deeper, wider, or both than the first channel.

[0212] Clause 7. The valve, in accordance with any of the preceding Clauses, wherein the compartment is cylindrical.

[0213] Clause 8. The valve of Clause 7, wherein the compartment has a circular, oval, oblong or polygonal cross-section.

[0214] Clause 9. A device comprising: the valve of any preceding Clause; and the upstream chamber, in which a portion of the upstream chamber adjacent to the first inlet of the first channel of the valve is tapered to smooth the transition between the upstream chamber and the first inlet of the first channel of the valve.

[0215] Clause 10. The device of Clause 9, in which the tapered portion of the upstream chamber has a trapezoidal cross-section parallel to the direction of flow.

[0216] Clause 11. The device of any of Clauses 910, in which the tapered portion of the upstream chamber is configured based, at least in part, on a fluid to be processed by the device.

[0217] Clause 12. The device of any of the Clauses 911, wherein 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 in relation to the first channel.

[0218] Clause 13. A device comprising: a rotating axis; and a channel for transferring a fluid by rotating the device around the Petition 870250101783, dated 06 / 11 / 2025, pp. 62 / 110 59 / 67 axis of rotation, the channel comprising an inlet, an outlet radially outward from the inlet relative to the axis of rotation 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 fluid transfer when the device rotates at a first speed, (ii) collect fluid residue when the device rotates at a second speed that is greater than the first speed and (iii) trap the collected fluid residue within the structure when the device is subjected to acceleration, deceleration or both.

[0219] Clause 14. The device of Clause 13, wherein the structure comprises: a compartment for containing the fluid residue; and a chamber connecting the compartment to the first side of the first portion of the channel and having a greater depth than the first portion of the channel and the compartment, thus acting as a valve between the first portion of the channel and the compartment.

[0220] Clause 15. The device of any of Clauses 1314, wherein: at least a portion of the structure is positioned radially outward from the first portion of the channel; and a radially more inward point at a junction formed by the chamber and the first side of the first portion of the channel defines a maximum allowable level for fluid residue.

[0221] Clause 16. The device, according to Clause 15, in which a second side of the first portion of the channel is positioned radially within the maximum permitted level for fluid residue.

[0222] Clause 17. The device, in accordance with any of Clauses 13-16, in which the first portion of the channel is folded.

[0223] Clause 18. The device comprising: a rotating shaft; and a mixing chamber having a curved side that is not coaxial with the rotating shaft and configured to mix a fluid with two or more different components by inertia.

[0224] Clause 19. A method comprising: (A) obtaining a Petition 870250101783, dated 06 / 11 / 2025, p. 63 / 110 60 / 67 device comprising a rotating axis and a mixing chamber with a curved side that is not coaxial with the rotating axis, wherein the mixing chamber contains a fluid comprising two or more different components; (B) accelerating the device into first gear in a direction towards the curved side of the mixing chamber; and (C) abruptly decelerating the device so that the fluid moves towards the curved side of the mixing chamber due to inertia, wherein the curved side of the mixing chamber translates the fluid motion in a circular motion that produces vortices, thus promoting the mixing of the two or more different components in the fluid.

[0225] Clause 20. The method of Clause 19, further comprising: (D) repeat the acceleration (B) and deceleration (C) one or more times.

[0226] Clause 21. The method of any of Clauses 19-20, where deceleration (C) causes the device to stop completely.

[0227] Clause 22. The method of any of Clauses 19-21, wherein the deceleration (C) is carried out 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 higher.

[0228] Clause 23. The method of any of Clauses 19-22, wherein a volume of fluid is at most 50%, at most 55%, at most 60%, at most 65% or at most 70% of the mixing chamber.

[0229] Clause 24. The method of any of Clauses 19-23, wherein the first velocity is based, at least in part, on a type of fluid, a quantity of fluid, a shape of the mixing chamber or any combination thereof.

[0230] Clause 25. The method of any of Clauses 19-24, wherein the mixing chamber comprises a path on a side opposite 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 towards the path; and (F) abruptly decelerating the device so that the fluid moves Petition 870250101783, dated 06 / 11 / 2025, pp. 64 / 110 61 / 67 towards the mixing chamber track due to inertia.

[0231] Clause 26. The method of Clause 25, in which the second velocity is based, at least in part, on a type of fluid, a quantity of fluid, a shape of the mixing chamber or any combination thereof.

[0232] Clause 27. A method comprising (A) obtaining a device having an axis of rotation and a chamber having a path that is not coaxial with the axis of rotation, wherein the chamber contains a fluid, (B) accelerating the device in a direction towards the chamber path and (C) abruptly decelerating the device so that the fluid moves towards the chamber path due to inertia.

[0233] Clause 28. A capillary channel comprising: an open end; a dead end positioned radially outward from the open end with respect to an axis of rotation; and first, second and third lanes, wherein the first lane has an inlet at the open end to receive a fluid; the third lane has an outlet at the open end to vent air; and the second lane is formed between and connected to the first and third lanes, wherein the second lane has a flow resistance different from the first and third lanes, thus allowing the fluid to flow first through the first lane from the open end to the dead end and then flow through the second lane, the third lane or both from the dead end to the open end to facilitate bubble-free initiation.

[0234] Clause 29. The capillary channel of Clause 28, wherein the first, second and third lanes collectively form a stepped cross-section perpendicular to a length direction of the capillary channel.

[0235] Clause 30. The capillary channel of Clause 29, where the first and third lanes are deeper than the second lane.

[0236] Clause 31. The capillary channel of Clause 30, where the first and third tracks are substantially the same as each other.

[0237] Clause 32. The capillary channel of Clause 30, where the first Petition 870250101783, dated 06 / 11 / 2025, pp. 65 / 110 Tracks 62 / 67 and the third track are different from each other.

[0238] Clause 33. The capillary channel of any of Clauses 29-32, where at least two of the first, second and third lanes have the same width.

[0239] Clause 34. The capillary channel of any of Clauses 29-33, where at least two of the first, second and third lanes have different widths.

[0240] Clause 35. A device comprising: a rotating shaft; a ventilation port; and the capillary channel of any of Clauses 28-34, wherein the outlet of the third track of the capillary channel is connected to the ventilation port.

[0241] Clause 36. A device comprising: a chamber; and a channel connected to the chamber for distributing a fluid to the chamber, wherein the chamber and the channel collectively form a junction that minimizes or eliminates capillary flow when the fluid exits from an outlet of the channel into the chamber.

[0242] Clause 37. The device of Clause 36, wherein the channel comprises a salient portion that forms at least a portion of the junction.

[0243] Clause 38. The device of Clause 37, wherein the projecting portion comprises a U-shaped wall on each side of the channel at the channel outlet.

[0244] Clause 39. The device of Clause 37, wherein the projecting portion comprises a V-shaped wall on each side of the channel at the channel outlet.

[0245] Clause 40. The device of any of Clauses 3639, in which a chamber wall adjacent to the channel outlet is curved radially inward relative to the channel outlet to form at least a portion of the junction.

[0246] Clause 41. The device of any of Clauses 3640, wherein: the junction allows fluid to flow from the channel outlet to the chamber in a direction of a centrifugal force. Petition 870250101783, dated 06 / 11 / 2025, pp. 66 / 110 63 / 67

[0247] Clause 42. A method comprising: (A) obtaining a device 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known; (B) measuring a first optical density of the absorbent dye in the first portion of the structure and a second optical density of the absorbent dye in the second portion of the structure; (C) calculating an optical density difference between the first and second optical densities; (D) calculating a ratio of the optical density difference to the nominal depth difference, wherein the ratio represents a product of an extinction coefficient and a concentration of the absorbent dye;and (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, a depth of any additional structure of the device, or any combination thereof.;

[0248] Clause 43. The method of Clause 42, wherein obtaining (A) comprises: obtaining the device with the structure; and filling the structure with the absorbent dye.

[0249] Clause 44. A device comprising: one or more structures, each comprising a first portion having a first depth and a second portion having a second depth, wherein the first and second depths are different from each other, but a nominal depth difference between the first and second depths is known, thus allowing the self-calibration of a depth of any structure of the device independently of variations in the manufacture of the device.

[0250] Clause 45. The device of Clause 44, in which one or more structures comprise a first structure and a second structure at different locations in the device. Petition 870250101783, dated 06 / 11 / 2025, pp. 67 / 110 64 / 67

[0251] Clause 46. The provision of Clause 45, in which the difference in nominal depth of the first structure is the same as the second structure.

[0252] Clause 47. The device of Clause 45, in which the nominal depth difference of the first structure is different from the second structure.

[0253] Clause 48. A method comprising: (A) obtaining a device comprising a structure located in a path 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known; (B) measuring a first optical density of the first component in the first portion of the structure and a second optical density of the first component in the second portion of the structure; (C) calculating an optical density difference between the first and second optical densities; 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.

[0254] Clause 49. The method of Clause 48, in which the concentration of the first component in the mixture is determined by comparing the difference in optical density with a calibration curve in an optical path corresponding to the nominal depth difference.

[0255] Clause 50. The method of Clause 49 further comprises: (E) creating, prior to determination (D), the calibration curve, wherein creation (E) comprises: (i) preparing a series of standard solutions with known concentrations of the first component; (ii) measuring the absorbance of each of the standard solutions at one or more wavelengths specific to the first component in one or more optical ways, thereby obtaining a plurality of absorbance values; and (iii) plotting the absorbance values ​​against the corresponding concentrations of the first component to create the Petition 870250101783, dated 06 / 11 / 2025, pp. 68 / 110 65 / 67 calibration curve for each of the one or more optical paths.

[0256] Clause 51. The method of Clause 50, in which the absorbance measurement is carried out using a spectrophotometer or a microfluidic device.

[0257] Clause 52. The method of Clause 48, wherein an extinction coefficient of the first component is known; and the concentration of the first component in the mixture is calculated by dividing the difference in optical density by the difference in nominal depth and the extinction coefficient of the first component.

[0258] Clause 53. The method of any of Clauses 48-52, wherein the first component is hemoglobin.

[0259] Clause 54. A device comprising: a structure located in a path 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known, thus allowing the measurement of a concentration of the first component independently of variations in the manufacture of the device.

[0260] Clause 55. A system for operating the device or performing the method, as per any preceding Clause. TERMINOLOGIES AND REFERENCES CITED

[0261] The terminology used in this document is intended to describe particular embodiments only and is not intended to limit disclosure. As used in the invention description and appended claims, the singular forms “a”, “an”, “the” and “the” are intended to include plural forms as well, unless the context clearly indicates otherwise. It will be understood that the terms left or right, top or bottom, inside or outside, inside or outside, etc. are used to describe features of the embodiments. Petition 870250101783, dated 06 / 11 / 2025, pp. 69 / 110 Figures 66 / 67 are illustrative with reference to the positions of such features, as shown in the figures. It will be understood that, although the terms first, second, etc. may be used in this document 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 could be called a second element and, similarly, a second element could be called a first element, without altering the meaning of the description, provided that the first element and the second element are renamed consistently.

[0262] As used in this document, the term and / or, as used in this document, refers to and encompasses any and all possible combinations of one or more of the associated listed items. It will further be understood that the terms include, includes, including, comprise, includes and / or comprising, when used in this descriptive report, specify the presence of declared resources, integers, steps, operations, elements and / or components, but do not exclude the presence or addition of one or more other resources, integers, steps, operations, elements, components and / or groups thereof.

[0263] The term about or approximately is used in this document to provide literal support for the exact number it precedes, as well as a number that is close to or approximately the number the term precedes. To determine whether a number is close to or approximately a specifically quoted number, the unquoted approximation or near number may be a number that, in the context in which it is presented, provides the substantial equivalent of the specifically quoted number. It should be appreciated that all numerical values ​​and ranges disclosed in this document are approximate values ​​and ranges, whether about is used in conjunction with them. It should also be appreciated that the term about, as used in this document, in conjunction with a numeral, refers to a value that may be ±0.01% (inclusive), ±0.1% (inclusive), ±0.5% (inclusive), ±1% (inclusive) Petition 870250101783, dated 06 / 11 / 2025, pp. 70 / 110 67 / 67 of that number, ±2% (inclusive) of that number, ±3% (inclusive) of that number, ±5% (inclusive) of that number, ±10% (inclusive) of that number, or ±15% (inclusive) of that number. It should also be noted that when a numerical range is disclosed in this document, any numerical value that falls within that range is also specifically disclosed.

[0264] The term "if" used in this document is optionally interpreted as meaning when or by or in response to the determination or in response to the detection or in accordance with a determination that, depending on the context. Similarly, the phrase "if it is determined" or "if [a stated condition or event] is detected" used in this document is optionally interpreted as meaning by determination or in response to the determination or by determination [of the stated condition or event] or in response to the detection [of the stated condition or event] or in accordance with a determination that [a stated condition or event] is detected, depending on the context.

[0265] When a reference number is given an i-th denotation, the reference number refers to a generic component, set, or modality. For example, an i-th unit refers to the i-th unit in a plurality of units.

[0266] All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent application or patent were specifically and individually indicated to be incorporated by reference in its entirety for all purposes.

Claims

1. A valve, characterized by 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 a flow direction that is the same as or smaller than the upstream chamber, thus 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 the first outlet of the first channel, thus forming a hydrophilic junction at the first outlet of the first channel.

2. A valve according to claim 1, further characterized by comprising: a second channel 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.

3. A valve according to claim 1, characterized in that the compartment is deeper, wider, or both than the first channel.

4. Device, characterized by comprising: the valve according to claim 1; and the upstream chamber, in which a portion of the upstream chamber adjacent to the first inlet of the first channel of the valve is tapered to smooth the transition between the upstream chamber and the first inlet of the first channel of the valve.

5. Device according to claim 4, characterized in that the tapered portion of the upstream chamber has a trapezoidal cross-section parallel to the flow direction.

6. Device, characterized by comprising: a rotation axis; and a channel for transferring a fluid by rotating the device around the axis of rotation, the channel comprising an inlet, an outlet radially outward from 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 fluid transfer when the device rotates at a first speed, (ii) collect fluid residue when the device rotates at a second speed that is greater than the first speed and (iii) trap the collected fluid residue within the structure when the device is subjected to acceleration, deceleration or both.

7. Device according to claim 6, characterized by the structure comprising: a bag to contain the fluid residue; and a chamber connecting the compartment to the first side of the first portion of the channel and having a greater depth than the first portion of the channel and the compartment, thus acting as a valve between the first portion of the channel and the compartment.

8. Device according to claim 6, characterized in that: at least one portion of the structure is positioned radially outward from the first portion of the channel; and a radially more inward point at a junction formed by the chamber and the first side of the first portion of the channel defines a maximum allowable level for fluid residue.

9. Device according to claim 8, characterized in that a second side of the first portion of the channel is positioned radially inward to the maximum permitted level for fluid residue.

10. Device according to claim 6, characterized in that the first portion of the channel is folded.

11. Method, characterized by comprising: (A) obtaining a device comprising a rotating axis and a mixing chamber with a curved side that is not coaxial with the rotating axis, Petition 870250081065, dated 09 / 09 / 2025, p. 122 / 128 3 / 7 wherein the mixing chamber contains a fluid comprising two or more different components; (B) accelerating the device to a first gear in a direction towards the curved side of the mixing chamber; and (C) abruptly decelerating the device so that the fluid moves towards the curved side of the mixing chamber due to inertia, wherein the curved side of the mixing chamber translates the fluid motion in a circular motion that produces vortices, thus promoting the mixing of the two or more different components in the fluid.

12. Method according to claim 11, characterized by further comprising: (D) repeating the acceleration (B) and deceleration (C) one or more times.

13. Method according to claim 12, characterized in that the mixing chamber comprises a path on a side opposite 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 towards the path; and (F) abruptly decelerating the device so that the fluid moves towards the path of the mixing chamber due to inertia.

14. Method, characterized by comprising: (A) obtaining a device having an axis of rotation and a chamber having a path that is not coaxial with the axis of rotation, wherein the chamber contains a fluid; (B) accelerating the device in a direction towards the path of the chamber; and (C) abruptly decelerating the device so that the fluid moves towards the path of the chamber due to inertia.

15. Capillary channel, characterized by comprising: an open end; Petition 870250081065, dated 09 / 09 / 2025, page 123 / 128 4 / 7 a dead end positioned radially outward from the open end with respect to an axis of rotation; and first, second and third lanes, wherein the first lane has an inlet at the open end to receive a fluid; the third lane has an outlet at the open end to vent air; and the second lane is formed between and connected to the first and third lanes, wherein the second lane has a different flow resistance from the first and third lanes, thus allowing the fluid to flow first through the first lane from the open end to the dead end and then flow through the second lane, the third lane or both from the dead end to the open end to facilitate bubble-free initiation.

16. Capillary channel, according to claim 15, characterized in that the first, second and third lanes collectively form a stepped cross-section perpendicular to a length direction of the capillary channel.

17. Capillary canal, according to claim 16, characterized in that the first and third lanes are deeper than the second lane.

18. Device characterized by comprising: a chamber; and a channel connected to the chamber for distributing a fluid to the chamber, wherein the chamber and the channel collectively form a junction that minimizes or eliminates capillary flow when the fluid exits from an outlet of the channel into the chamber.

19. Device according to claim 18, characterized in that the channel comprises a protruding portion that forms at least a portion of the junction.

20. Device according to claim 19, characterized by the projecting portion comprising a U-shaped or V-shaped wall on each side of the channel at the channel outlet. Petition 870250081065, dated 09 / 09 / 2025, pp. 124 / 128 5 / 7 21. Device according to claim 20, characterized in that a chamber wall adjacent to the channel outlet is curved radially inward relative to the channel outlet to form at least a portion of the junction.

22. Device according to claim 21, characterized in that: the junction allows fluid to flow from the channel outlet to the chamber in a direction of centrifugal force.

23. Method, characterized by comprising: (A) obtaining a device 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known; (B) measuring a first optical density of the absorbent dye in the first portion of the structure and a second optical density of the absorbent dye in the second portion of the structure; (C) calculating an optical density difference between the first and second optical densities; (D) calculating a ratio of the optical density difference to the nominal depth difference, wherein the ratio represents a product of an extinction coefficient and a concentration of the absorbent dye;and (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, a depth of any additional structure of the device, or any combination thereof.

24. Method according to claim 23, characterized by obtaining (A) comprising: obtaining the device with the structure; and filling the structure with the absorbent dye. Petition 870250081065, dated 09 / 09 / 2025, pp. 125 / 128 6 / 7 25. Device, characterized by comprising: one or more structures, each comprising a first portion having a first depth and a second portion having a second depth, wherein the first and second depths are different from each other, but a nominal depth difference between the first and second depths is known, thus allowing the self-calibration of a depth of any structure of the device independently of variations in the manufacture of the device.

26. Device according to claim 25, characterized in that one or more structures comprise a first structure and a second structure at different locations in the device.

27. Method, characterized by comprising: (A) obtaining a device comprising a structure located in a path 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 and second depths are different from each other, but the nominal depth difference between the first and second depths is known; (B) measuring a first optical density of the first component in the first portion of the structure and a second optical density of the first component in the second portion of the structure; (C) calculating an optical density difference between the first and second optical densities; 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.

28. Method according to claim 27, characterized in that the concentration of the first component in the mixture is determined by comparing the difference in optical density with a calibration curve in an optical path corresponding to the nominal depth difference. Petition 870250081065, dated 09 / 09 / 2025, pp. 126 / 128 7 / 7 29. Method according to claim 28, characterized by further comprising: (E) creating, prior to determination (D), the calibration curve, wherein the creation (E) comprises: (i) preparing a series of standard solutions with known concentrations of the first component; (ii) measuring the absorbance of each of the standard solutions at one or more wavelengths specific to the first component in one or more optical ways, thereby obtaining 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 ways.

30. Method according to claim 27, characterized in that: an extinction coefficient of the first component is known; and the concentration of the first component in the mixture is calculated by dividing the difference in optical density by the difference in nominal depth and the extinction coefficient of the first component.

31. Capillary channel, according to any one of claims 15 to 17, characterized in that a biological sample comprising a mixture of aqueous and non-aqueous biological components is moved from an entry port to an external measuring chamber by means of inertial and centrifugal forces for analysis and evaluation.

32. Capillary channel, according to claim 31, characterized in that the mixture is a mixture of body fluids and cells.

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