Fluid device
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Filing Date
- 2023-05-12
- Publication Date
- 2026-05-08
AI Technical Summary
Microfluidic devices face issues with air voids and uneven solution distribution due to resistance at wall surfaces, leading to unbalanced solution distribution and inefficient fluid exchange, which significantly impact measurement results as device sizes decrease.
A disc-shaped fluidic device with a fluid inlet configured to introduce fluid tangentially at the zero o'clock position and a fluid outlet directing fluid from the 6 o'clock to 12 o'clock position, enhancing fluid exchange efficiency and minimizing air voids.
This configuration enables efficient and accurate measurements on small sample volumes by reducing air voids and improving solution distribution, maintaining high sensing performance even at low fluid volumes.
Abstract
Description
Fluidic Devices
[0001] The present disclosure relates to fluidic devices.
[0002] Microfluidic devices with small volumes have been developed to perform measurements on small liquid samples.
[0003] When a fluid is introduced into a fluidic device, voids or dead spaces tend to form in the corners of the space. Furthermore, due to the resistance of the walls, the target solution may be introduced relatively close to the center of the volume, while the previous liquid may remain near the walls. This results in an uneven distribution of the solution within the fluidic device. As long as the volume of the fluidic device is large, these problems only have a small effect on the measurement results, and measurements can be performed in areas where no problems exist. In other words, these problems can be ignored.
[0004] However, as flow channel devices become smaller, the occurrence or persistence of air voids or uneven distribution of the target solution becomes larger relative to the measurement area or volume, and further, the behavior of the fluid in the microspace becomes more pronounced. Therefore, these problems can substantially affect the measurement results or measurement efficiency of microfluidics. However, these problems are merely examples, and the problem of the present disclosure described below is not limited to these.
[0005] Therefore, it is desirable to reduce the occurrence or persistence of voids and improve the efficiency of fluid exchange in microfluidic devices. The present disclosure describes and provides microfluidic devices that reduce or avoid these and other problems.
[0006] In one embodiment of the present disclosure, a fluidic device is provided, comprising: a device body having a disk-shaped space for containing a fluid therein; a fluid inlet configured to introduce the fluid in a clockwise and tangential direction at substantially the 0 o'clock position on the circumference of the disk-shaped space; and a fluid outlet configured to discharge the fluid from the space at substantially the 6 o'clock to 12 o'clock position on the circumference of the disk-shaped space.
[0007] According to some embodiments of the present disclosure, for example, highly accurate measurements can be efficiently performed on relatively small sample volumes.
[0008]
[0013] Further aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the present disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.
[0009] 1 is a top view schematically showing a fluidic device according to a comparative example; FIG. 2 is a top view schematically showing a fluidic device according to a comparative example; FIG. 3 is a top view schematically showing a fluidic device according to some embodiments; FIG. 4 is a top view schematically showing a fluidic device according to some embodiments; FIG. 5 is a top view (A) and a perspective view (B) schematically showing a fluidic device according to an embodiment; FIG. 6 is a top view (A) and a perspective view (B) schematically showing a fluidic device according to an embodiment; FIG. 7 is a top view schematically showing a fluidic device according to an embodiment; FIG. 8 is an exploded perspective view of a fluidic device according to an embodiment; FIG. 9 is a top view schematically showing a fluidic device according to a comparative example; FIG. 10 is a graph showing output versus introduction amount for a fluidic device according to an embodiment and a fluidic device according to a comparative example; FIG. 11 is a graph showing time changes in output at each height of the disk-shaped space according to an example; FIG. 12 is a graph showing the relationship between height of the disk-shaped space and the time for which maximum output is maintained according to an example.
[0010] As used herein, the term "disc-shaped space" generally refers to a cylindrical space. The cross-sectional size of the cylinder (the size of the major and / or minor axes, the diameter or the radius) is the same as or larger than the size in the central axis direction. In some embodiments, the cylinder of the "disc-shaped space" has a substantially circular cross-section, and its diameter or radius is larger than the size in the central axis direction (the height of the disc-shaped space).
[0011] A "fluid inlet" (also referred to as a "fluid inlet" or "inlet") and / or a "fluid outlet" (also referred to as a "fluid outlet" or "outlet") has a tubular space (flow path) inside, and may be detachably connected to the device body, may be fixed to the device body, or may be formed or manufactured integrally with the device body. The inlet and / or outlet may refer to the flow path itself.
[0012] As used herein, zero o'clock refers to the angular position of the disc space where the fluid flowing from the fluid inlet substantially enters the disc space. Zero o'clock may be defined as the direction from the center of the disc space toward the connection point of the fluid inlet to the disc space. Zero o'clock may also be defined as the radial direction perpendicular to the circumferential direction at the time of fluid introduction. The introduced fluid, or at least a portion of it, flows circumferentially near the circumference of the disc-shaped space. In this specification, this flow direction is defined as clockwise.
[0013] The inlets and / or outlets are located at, substantially at, or near the circumference of the disk. As used herein, "circumference" refers to the circumference of the disk of the disk-shaped space of the fluidic device or its vicinity. This does not refer to a location on the geometric circumference, but rather to a position or location that is at least a distance away from the geometric circumference required to introduce or withdraw fluid into or from the disk-shaped space. For example, the inlets and / or outlets have a tubular structure, and at least a portion or all of the diameter of the tubular structure is within the disk. In this case, the center of the inlet or outlet tube does not lie on the circumference of the disk. Alternatively, due to manufacturing factors, it may not be possible to form the inlets and / or outlets on the circumference or their outer edges exactly on the circumference.
[0014] A "disc-shaped space" refers to a space formed in a cylindrical shape. In some embodiments, a cross section perpendicular to the central axis of the cylinder may be a perfect circle. In some embodiments, the cross section of the cylinder may be a non-perfect circle, for example, an ellipse. The circumferential surface of the disk-shaped space may be formed as a substantially curved surface, preferably a continuous curved surface.
[0015] In some embodiments, the fluid inlet may be configured to introduce fluid perpendicular to the cylindrical central axis of the disk-shaped space, i.e., in the plane of the disk. In some aspects, the fluid inlet may be connected to the side of the disk from outside the disk-shaped space.
[0016] In some embodiments, the fluid inlet may be configured to introduce fluid perpendicular to the central axis of the cylinder of the disk-shaped space, i.e., in a direction tilted from the in-plane direction of the disk. In some aspects, the fluid inlet may be connected to the bottom surface of the cylinder. In some aspects, the fluid inlet may be connected to the bottom surface of the cylinder in a direction non-perpendicular or tilted relative to the bottom surface. That is, the direction of the fluid inlet projected onto the bottom surface of the cylinder faces the circumferential direction of the cylinder.
[0017] In some embodiments, the angled inlet and outlet may be connected to the same bottom surface of the disk-shaped space, or in some embodiments, the angled inlet may be connected to a first bottom surface (one of the bottom surfaces) and the outlet may be connected to a second bottom surface (the other of the bottom surfaces).
[0018] In some embodiments, the two bottom surfaces do not necessarily have to be parallel. For example, the bottom surfaces do not have to be flat. For example, at least a portion may be formed in a cone shape (convex or concave relative to the disk space). For example, one bottom surface of the cylinder may be configured to move away from the other bottom surface near the fluid inlet (convex cone). This makes it easier for air bubbles in the disk space to exit through the fluid outlet. For example, one bottom surface of the cylinder may be configured to move closer to the other bottom surface near the fluid inlet (concave cone). Fluid introduced into the disk space is more likely to pass near the circumference. The water flow on the circumferential side, which has a relatively small solution exchange rate, can be strengthened to increase the solution exchange rate.
[0019] The height of the disk-shaped space may be 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 150 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1000 μm, etc. or greater.
[0020] The height of the disk-shaped space may be 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 60 μm, 70 μm, 80 μm, 90 μm, 100 μm, 150 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1000 μm, 1.5 mm, 2 mm, etc., or smaller values.
[0021] The radial or planar feature of the disk-shaped space may be 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, or a larger value.
[0022] The radial or surface direction characteristic of the disk-shaped space may be a value such as 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 16 mm, 17 mm, 18 mm, 19 mm, 20 mm, or a smaller value.
[0023] The volume of the disk-shaped space may be 1 μL, 2 μL, 3 μL, 4 μL, 5 μL, 6 μL, 7 μL, 8 μL, 9 μL, 10 μL, 15 μL, 20 μL, 30 μL, 40 μL, 50 μL, 60 μL, 70 μL, 80 μL, 90 μL, 100 μL, 200 μL, 300 μL, 400 μL, 500 μL, etc., or greater.
[0024] The volume of the disk-shaped space may be 5 μL, 6 μL, 7 μL, 8 μL, 9 μL, 10 μL, 15 μL, 20 μL, 30 μL, 40 μL, 50 μL, 60 μL, 70 μL, 80 μL, 90 μL, 100 μL, 200 μL, 300 μL, 400 μL, 500 μL, 1 mL, etc., or smaller values.
[0025] The fluid inlet may have a volume that is substantially 50% to 200% of the volume of the disk-shaped space. The volume of the fluid inlet may be substantially 50%, 100%, 150%, or 200% of the volume of the disk-shaped space. The sum of the volume of the disk-shaped space and the volume of the inlet (the volume from the fluid introduction point to the inlet to the disk-shaped space) may be 2 μL, 3 μL, 4 μL, 5 μL, 6 μL, 7 μL, 8 μL, 9 μL, 10 μL, etc., or a larger value. The sum of the volume of the disk-shaped space and the volume of the inlet may be 10 μL, 15 μL, 20 μL, 30 μL, 40 μL, 50 μL, etc., or a smaller value.
[0026] In some embodiments, the fluidic device may have a sensor on an inner wall of the disc-shaped space, hi some embodiments, the sensor may be located on one or both bottom inner walls of the disc-shaped space.
[0027] <Measurement Subject> In some embodiments, the subject (test subject) may include or may be a human. In some embodiments, the subject may include or may be a non-human animal. The subject may include or may be a mammal. The subject may be, for example, but not limited to, a working animal, a livestock animal, a pet, or a wild animal.
[0028] The sample to be measured may be a solution. The "solution" may be a body fluid, a solution derived from a body fluid, or a diluted solution of a body fluid. The solution may be a solution that is not a body fluid (non-body fluid-derived), or a mixture of a body fluid or a body fluid-derived solution and a non-body fluid-derived solution. The solution may be a solution used for sample measurement, or a solution used for calibration measurement. For example, the solution may be a standard solution or a calibration solution. For example, the solution may be a liquid that does not intentionally or deliberately contain the substance to be measured, so that it is used for calibration, etc. The sample to be measured may be a specimen. The solution may be a solution containing a chemical substance.
[0029] The "body fluid" may be lymph, tissue fluid such as interstitial fluid, intercellular fluid, or interstitial fluid, or may be body cavity fluid, serous cavity fluid, pleural fluid, ascites, pericardial fluid, cerebrospinal fluid (spinal fluid), synovial fluid, or aqueous humor (aqueous humor). The body fluid may be digestive fluid such as saliva, gastric juice, bile, pancreatic juice, or intestinal fluid, or may be sweat, tears, nasal mucus, urine, semen, vaginal fluid, amniotic fluid, or milk. The body fluid may be animal or human. The "body fluid" may also be a solution. The solution may contain a physiological buffer solution such as phosphate-buffered saline (PBS) or N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid buffer (TES) containing the substance to be measured. The solution is not particularly limited as long as it contains the substance to be measured.
[0030] The solution may contain a target substance. The solution may potentially contain a target substance. In some embodiments, the target substance may be a molecule, ion, polymer, biomolecule, etc. The target substance may comprise a biomolecule. The target substance may be a protein, a glycated protein, etc. For example, the solution may be tears, and the target substance may be albumin, glycated albumin, hemoglobin, or glycated hemoglobin contained in tears. Alternatively, the target substance may be albumin, glycated albumin, hemoglobin, or glycated hemoglobin in blood, serum, or plasma, or may be albumin, glycated albumin, hemoglobin, or glycated hemoglobin in interstitial fluid, urine, or saliva. Albumin may be oxidized albumin (HNA) or reduced albumin (HMA). In some embodiments, the substance to be measured may be AGEs (Advanced Glycation End Products). In some embodiments, the substance to be measured may be glycated lipids.
[0031] <Sensor> The sensor may be a chemical sensor, a biosensor, an ion sensor, etc. (hereinafter, these may be referred to as a "sensor," a "biochemical sensor," a "chemical sensor," or an "electrochemical sensor.") The sensor may include a plurality of sensors.
[0032] The sensor may include an electrode. The electrode may be an amperometric electrode. The electrode may include a hydrogen peroxide electrode. The electrode may include an oxygen electrode. The electrode may be a potentiometric electrode. The electrode may be an electrode for detecting ions (such as a pH electrode, a cyanide ion electrode, or an iodide ion electrode).
[0033] In some embodiments, the sensor may output an electrical signal. In some aspects, the sensor may output a current signal. The sensor may output a voltage signal or a charge. The sensor may be electrically connected to an ammeter, voltmeter, or the like.
[0034] In some embodiments, the sensor may have an enzyme membrane over the electrode.
[0035] In some embodiments, the enzyme membrane may contain a protease. "Protease" is generally a general term for peptide bond hydrolases that hydrolyze and catabolize proteins and polypeptides. A protease may be an enzyme that breaks down a protein into peptide fragments. When a protein contains glycated amino acid residues, the peptide fragments generated by the action of the protease may include peptide fragments containing glycated amino acid residues and peptide fragments that are not glycated at all.
[0036] The "protease" may be an animal-derived protease, a plant-derived protease, or a microbial-derived protease. The protease may be an exopeptidase or an endopeptidase. The protease may be an aspartic protease, a metalloprotease, a serine protease, or a thiol protease.
[0037] The term "protease" may include multiple types or kinds of proteases, or may include a single type or kind of protease. For example, the protease may include either a proteinase or a peptidase, or both. Mixing multiple proteases may increase the decomposition efficiency. The protease may include a modified protease or a modified protease. The protease may be used together with an additive. The additive may be, for example, a surfactant or urea. The additive may, for example, be capable of destabilizing or denaturing the protein. The use of a modified protease or an additive may, for example, be capable of improving the decomposition efficiency of the protein or the substrate selectivity, for example, but not limited to these.
[0038] A "substrate" is a substance that causes an enzyme to catalyze a chemical reaction. Alternatively, a substrate is a substance that binds to an enzyme protein and undergoes a reduction in the activation energy of a specific chemical reaction, resulting in its conversion to a specific product at a remarkable rate.
[0039] In some embodiments, the enzyme membrane may include an oxidase. An "oxidase" is an enzyme that uses molecular oxygen as a substrate for electron acceptors. Alternatively, an oxidase is an enzyme that catalyzes an oxidation-reduction reaction in which molecular oxygen is used as a hydrogen or electron acceptor.
[0040] In some embodiments, the oxidase may comprise a ketoamine oxidase. In some embodiments, the oxidase may comprise a glucose oxidase, which may be used to measure the glucose concentration in a sample. In this case, the substrate may comprise glucose. In some embodiments, the oxidase may comprise an alcohol oxidase, which may be used to measure the alcohol concentration in a sample.
[0041] "Ketoamine oxidase" generally refers to an oxidase that recognizes the ketoamine structure of a glycated amino acid or a peptide or peptide fragment containing a glycated amino acid residue and oxidizes the glycated amino acid to produce an amino acid, glucosone (α-ketoaldehyde), and hydrogen peroxide. Thus, ketoamine oxidase produces hydrogen peroxide at a concentration proportional to or related to the concentration of the glycated amino acid or peptide or peptide fragment containing the glycated amino acid residue that it recognizes.
[0042] The ketoamine oxidase may be a dehydrogenase, a kinase, or an oxidase, and may be fructosyl amino acid oxidase (FAOD), fructosyl peptide oxidase, fructosyl valylhistidine oxidase, fructosyl amine oxidase, amadoriase, fructosyl amine deglycase, or modified forms thereof.
[0043] In some embodiments, the sensor can measure glycated proteins. In some embodiments, a protease and a ketoamine oxidase may be disposed on or near the surface of an electrode. In some embodiments, an enzyme membrane may comprise a protease and a ketoamine oxidase. A typical enzymatic method for measuring glycated proteins involves first decomposing proteins into amino acids with a protease in a first step, treating only the glycated amino acids among the amino acids with ketoamine oxidase to generate hydrogen peroxide in a second step, and then optically or electrically measuring the hydrogen peroxide in a third step.
[0044] In some embodiments, the sensor may include a detection unit. The detection unit may be a hydrogen peroxide detection unit. The "hydrogen peroxide detection unit" (hydrogen peroxide sensor) may be an electrochemical electrode or a hydrogen peroxide electrode. The hydrogen peroxide electrode may have a counter electrode, a reference electrode, and a working electrode. In certain embodiments, the detection unit may detect oxygen. For example, it may detect the amount or concentration of oxygen reduced by an enzyme reaction. Oxygen detection is considered to be relatively insensitive to molecules and ions that are noise sources and resistant to interference. Oxygen consumption may be measured by detecting oxygen. Since the detection unit is saturated with air, it may be used for enzyme sensing. The detection unit may be configured to perform multiple detection methods selectively or in combination.
[0045] Optical Measurement In some embodiments, the fluidic device body may be configured to allow light to be guided from the outside into the disk-shaped space. The fluidic device body may be at least partially transparent.
[0046] The fluidic device may comprise an optical device or may be configured to be connected to an optical device.
[0047] As used herein, "optical measurement" generally refers to determining an optical property of a substance using an optical element or device. In some embodiments, an optical measurement of a substance of interest may be measured. In some aspects, a property of a substance bound to or associated with the substance of interest (hereinafter, not the substance of interest itself, but a substance (e.g., a reagent) that is chemically, biologically, or physically bound to or associated with the substance of interest) may be measured. A property of a reagent may be measured. The reagent may be referred to as the "substance of interest."
[0048] In some embodiments, the optical measurement may include a spectroscopic measurement. For example, the absorbance of the substance of interest may be measured. In some embodiments, a color indicator corresponding to the substance of interest may be introduced. The color indicator may be detected or measured.
[0049] The fluidic device may include a plurality of disk-shaped spaces. Each disk may include an inlet and an outlet. Fluid may be provided to the plurality of inlets and disk-shaped spaces from a common flow path. Fluid may be provided to each of the plurality of inlets and disk-shaped spaces individually. The plurality of disk-shaped spaces included in the fluidic device may have substantially the same volume, or may have different volumes among them.
[0050] In some embodiments, the fluidic device may be a stop-flow fluidic device. After the introduced fluid fills the disc-shaped space, the introduction of the fluid may be stopped. Then, a predetermined measurement or sensing may be performed on the fluid in the disc-shaped space.
[0051] In some embodiments, predetermined measurements or sensing may be performed on the fluid in the disc-shaped space while the introduced fluid is flowing through the disc-shaped space.
[0052] Comparative Example 1 Fig. 1A is a schematic diagram of a fluidic device 100 as a comparative example. The fluidic device 100 has a disk-shaped space 120 formed in a main body 110. A fluid inlet 130 and a fluid outlet 140 are fluidly connected to the disk-shaped space 120. The fluid inlet 130 in Fig. 1A is arranged in a cross-sectional direction. A fluid 151 (solid arrow) that passes through the fluid inlet 130 is introduced into the disk-shaped space 120 perpendicular to the 0 o'clock direction, i.e., in the circumferential direction. The fluid outlet 140 in Fig. 1A is arranged approximately at the center of the disk-shaped space 120 and discharges the internal fluid from the bottom surface (not shown) to the outside of the disk-shaped space 120.
[0053] 1A shows a cross section perpendicular to the central axis of the disk-shaped space 120. The fluid outlet 140 is actually connected to one of the bottom surfaces of the disk-shaped space 120 and is not present on the cross section, but is shown in the same figure for the sake of explanation. The same applies to the following figures.
[0054] FIG. 1B shows the same fluidic device 100 as in FIG. 1A and will be used to explain an example of the flow of a fluid 151 within the disk-shaped space 120. After entering the disk-shaped space 120 through the fluid inlet 130, the fluid 151 flows around the circumference (see dashed line 152). However, the fluid outlet 140 is located at the center of the disk-shaped space 120. Therefore, the fluid 152 flowing around the circumference leaves the circumference, for example, between 6 o'clock and 9 o'clock, without going around the circumference. The fluid 152 then flows toward the fluid outlet 140 located at the center of the disk-shaped space 120, or is pulled by the fluid outlet 140. As a result, a liquid level 153 is formed, and a space 154 (sometimes called a bubble) without liquid is formed around this boundary. As a result, the disk-shaped space 120, especially its bottom surface, cannot be completely filled with fluid.
[0055] Comparative Example 2 Fig. 2A shows a schematic diagram of a fluidic device 200 as a comparative example. The fluidic device 200 has a disk-shaped space 220 formed in a main body 210. A fluid inlet 230 and a fluid outlet 240 are fluidly connected to the disk-shaped space 220. The fluid inlet 230 in Fig. 2A is arranged in a cross-sectional direction. A fluid 251 (solid arrow) that passes through the fluid inlet 230 is introduced into the disk-shaped space 220 perpendicular to the 0 o'clock direction, i.e., in the circumferential direction. The fluid outlet 240 in Fig. 2A is arranged at the 3 o'clock position near the circumference of the disk-shaped space 220, and discharges the internal fluid from the bottom (not shown) to the outside of the disk-shaped space 220.
[0056] FIG. 2B shows the same fluidic device 200 as FIG. 2A and will be used to explain an example of the flow of fluid 251 within the disk-shaped space 220. After entering the disk-shaped space 220 through the fluid inlet 230, the fluid 251 flows around the circumference (see dashed line 252). The fluid outlet 240 is located at the 3 o'clock position of the disk-shaped space 220. The fluid 252 that flows around the circumference exits partially at the fluid outlet 240, while the remainder continues to flow along the circumference. However, the fluid 252 does not go around the circumference completely; instead, it leaves the circumference, for example, between 6 o'clock and 9 o'clock. The fluid 252 then flows toward the fluid outlet 240 or is pulled toward the fluid outlet 240. As a result, a liquid level 253 is formed, and a space 254 (sometimes called a bubble) without liquid is formed around this boundary. As a result, the disk-shaped space 220, especially its bottom surface, cannot be completely filled with fluid.
[0057] The fluid 152, 252 (flow indicated by dashed lines) within the disk-shaped space 120, 220 shown in Figures 1 and 2 is illustrative and should not be construed as limiting. Other fluid flows are possible. In some embodiments, the introduced fluid may completely fill the disk-shaped space 120, 220.
[0058] <Configuration of Fluidic Device> Figures 3A to 3D show configurations of fluidic devices according to some embodiments. Figure 3A shows a fluidic device 300 in which the fluid outlet 340 is located at the 6 o'clock position near the circumference of the disc-shaped space 320. Figure 3B shows a fluidic device 400 in which the fluid outlet 440 is located at approximately the 7:30 position near the circumference of the disc-shaped space 420. Figure 3C shows a fluidic device 500 in which the fluid outlet 540 is located at the 9 o'clock position near the circumference of the disc-shaped space 520. In general, the closer the fluid outlet is to the fluid inlet, the less likely air bubbles will remain in the disc-shaped space.
[0059] FIG. 3D shows a fluidic device 600 in which the fluid outlet 640 is located near the circumference of the disk-shaped space 620, at approximately the 10 o'clock position. The outlet 640 in FIG. 3D is located as close to the fluid inlet 630 as possible without interfering with the fluid inlet 630. At this location, the fluid introduced through the fluid inlet 630 meets the fluid flowing along the circumference of the disk-shaped space 620, creating a turbulent flow. Therefore, air (liquid-free space or bubbles) is likely to remain. The fluid outlet 640 can efficiently expel the bubbles seen in FIGS. 1B and 2B to the outside.
[0060] As shown in Figures 1 to 3, the cross section of the disc-shaped space may be circular. Alternatively, the cross section of the disc-shaped space may not be circular, but may be other curved lines or may be composed of multiple curved surfaces. In some embodiments, the cross section of the disc-shaped space may be elliptical.
[0061] 4A and 4B show fluidic devices 700 and 800 having an elliptical disk-shaped space. The fluidic device 700 shown in FIG. 4A has a major axis of the ellipse extending from 0 o'clock to 6 o'clock relative to the disk-shaped space 720. Fluid 751 is introduced into the disk-shaped space 720 circumferentially by a fluid inlet 730 at the 0 o'clock position, which is one end of the major axis. The fluidic device 800 shown in FIG. 4B has a major axis of the ellipse extending from 3 o'clock to 9 o'clock relative to the disk-shaped space 820. Fluid 851 is introduced into the disk-shaped space 820 circumferentially by a fluid inlet 830 at the 0 o'clock position, which is one end of the minor axis. In either case, the fluid outlets 740 and 840 are located at approximately 10 o'clock or in a position close to the fluid inlets 730 and 830 so as not to interfere with them.
[0062] In some embodiments, the fluid inlet may be positioned in-plane of the cross-section of the disc-shaped space, hi some embodiments, the fluid inlet may be positioned at an angle to the cross-section of the disc-shaped space.
[0063] Figure 5 shows a fluidic device 900 according to one embodiment, in which the fluid inlet is oriented in the plane of the cross section of the disk-shaped space. Figure 5A shows a cross section parallel to the bottom surface of the fluidic device 900, or a top view. Figure 5B shows a perspective view of the fluidic device 900, with the main body 910 omitted. The fluidic device 900 has a fluid inlet 930 oriented in the plane parallel to the bottom surface of the disk-shaped space 920.
[0064] The fluid inlet 930 introduces a fluid 951 into the disk-shaped space 920 in the in-plane direction at the 0 o'clock position (actually, the position is from close to 11 o'clock to 0 o'clock (12 o'clock)). The fluid (dashed line 952) flows mainly circumferentially within the disk-shaped space 920, filling it. The fluid 952 finally exits from a fluid outlet 940 arranged approximately vertically from one bottom surface of the disk-shaped space 920.
[0065] Figure 6 shows an embodiment of a fluidic device 1000 in which the fluid inlet is positioned at an angle relative to the cross-section of the disk-shaped space. Figure 6A shows a cross-section parallel to the bottom surface of the fluidic device 1000, or a top view. Figure 6B shows a perspective view of the fluidic device 1000, with the main body 1010 omitted. The fluidic device 1000 has a fluid inlet 1030 positioned at an angle θ relative to the bottom surface of the disk-shaped space 1020.
[0066] The fluid inlet 1030 introduces fluid 1051 into the disk-shaped space 1020 from a direction of angle θ at the 0 o'clock position of the disk-shaped space 1020 (actually, the position is from close to 11 o'clock to 0 o'clock (12 o'clock)). The fluid (dashed line 1052) flows mainly circumferentially within the disk-shaped space 1020, filling it. The fluid 1052 finally exits from one of the bottom surfaces of the disk-shaped space 1020 through a fluid outlet 1040 arranged approximately vertically.
[0067] <Fluidic Device-1 with Sensor> In some embodiments, the fluidic device may have a sensor inside the disk-shaped space. The sensor can sense the fluid introduced into the disk-shaped space or a substance contained in the fluid.
[0068] 7 shows a top view of a fluidic device 1100 according to one embodiment, where the solid and dashed lines are not to be interpreted as corresponding to whether they are visible from the top, but merely serve to show a schematic representation of the configuration of components within the fluidic device 1100.
[0069] The fluidic device 1100 has a disk-shaped space 1120 inside the main body 1110. A fluid inlet 1130 and a fluid outlet 1140 are formed in the disk-shaped space 1120. The fluid inlet 1130 is disposed at an angle with respect to the bottom surface of the disk-shaped space 1120, and the fluid outlet 1140 is disposed perpendicular to the bottom surface of the disk-shaped space 1120. A fluid introduction port 1131 is formed perpendicular to the plane of the main body 1110 or the disk-shaped space 1120, and introduces a fluid introduced from the outside into the fluid introduction port 1131. The fluid then enters the fluid inlet 1130 and is introduced into the disk-shaped space 1120 from an oblique direction. The fluid outlet 1140 is formed perpendicular to the plane of the main body 1110 or the disk-shaped space 1120. The fluid is discharged from the disk-shaped space 1120 to the outside via the fluid outlet 1140.
[0070] Sensing electrodes 1121, 1122, and 1123 are disposed in the disk-shaped space 1120. In this embodiment, the sensing electrodes are three-electrode electrodes for electrochemical measurement. The sensing electrodes include a working electrode 1121, a counter electrode 1122, and a reference electrode 1123. These electrodes are connected to corresponding connection terminals 1161, 1162, and 1163 via lead wires. The connection terminals are exposed on the outer surface of the main body 1110, allowing electrical connection to be made from the outside.
[0071] 8 shows an exploded perspective view of a fluidic device 2000 according to one embodiment. From top to bottom, the fluidic device 2000 includes a pipette port 2100, an upper seal 2200, a flow path cell 2300, an adhesive film 2400, a sensor chip 2500, a sensor chip support 2600, an O-ring 2700, and a waste tank 2800, which are arranged in a vertical combination.
[0072] The sensor chip support 2600 has a sensor chip receiving portion 2680, and the sensor chip 2500 is placed therein. The flow path cell 2300 is attached to the sensor chip support 2600 via an adhesive film 2400.
[0073] The flow path cell 2300 has a disk-shaped recess 2320 on its lower surface. This disk-shaped recess 2320, the surface of the electrode section 2520 on the upper surface of the sensor chip 2500 facing it, and the through-hole 2320 of the adhesive film 2400 sandwiched between them define a disk-shaped space.
[0074] The top seal 2200 is adhered and sealed to the top surface of the flow-path cell 2300. The pipette port 2100 is placed on top of this.
[0075] The pipette port 2100 has a fluid inlet channel 2130 in the center and a pipette receiving portion 2131 that receives the tip of a pipette and continues to the fluid inlet channel 2130. The top seal 2200 has a channel inlet hole 2230 that leads from the pipette port 2100 to the channel cell 2300.
[0076] The sensor chip support 2600 is pressed against the waste liquid tank 2800 via the O-ring 2700. The flow path cell 2300 above it has mating claws 2380, which mate with claw receivers 2880 of the waste liquid tank 2800. As a result, the pipette port 2100, top seal 2200, flow path cell 2300, adhesive film 2400, sensor chip 2500, and sensor chip support 2600, which are assembled by bonding, are tightly attached to the waste liquid tank 2800.
[0077] The fluid inlet channel 2130 of the pipette port 2100, the channel inlet hole 2230 of the top seal 2200, and the top opening of the fluid inlet 2330 of the flow path cell 2300 are aligned. This allows fluid introduced from a pipette (not shown) to pass through the fluid inlet channel 2130 of the pipette port 2100, the channel inlet hole 2230 of the top seal 2200, and the fluid inlet 2330 of the flow path cell 2300, and into the disk-shaped space 2320.
[0078] The contact openings 2260 of the top seal 2200, the contact through-holes 2360 of the flow path cell 2300, and the contact openings 2460 of the adhesive film 2400 are aligned so as to be positioned above the contact terminals 2560 of the sensor chip 2500. This allows connection pins (not shown) to approach and electrically connect to the contact terminals 2560 of the sensor chip 2500 from outside the fluidic device 2000 through these openings and through-holes. In this way, surface electrochemical measurements can be performed on the introduced liquid via the electrode portions 2520 of the sensor chip 2500, and electrical signals can be obtained.
[0079] The fluid (waste liquid) coming out of the disk-shaped space 2320 of the flow path cell 2300 rises through the fluid outlet 2340 of the flow path cell 2300, passes through a passage 2341 formed by a groove 2341 in the upper surface of the flow path cell 2300 and sealed by the upper surface seal 2200, and is guided downward through the second fluid outlet 2342. The waste liquid then passes through the through-hole 2440 in the adhesive film and the through-hole 2640 in the sensor chip support 2600, and falls into the waste liquid storage space 2840 of the waste liquid tank 2800, where it is collected in a sealed manner.
[0080] The air opening 2270 of the top seal 2200, the air through hole 2370 of the flow path cell 2300, the air opening 2470 of the adhesive film 2400, and the air through hole 2670 of the sensor chip support 2600 are aligned. That is, the waste liquid storage space 2840 of the waste liquid tank 2800 is fluidly connected to the outside of the fluidic device 2000, forming an air vent. As a result, as waste liquid is introduced into the waste liquid storage space 2840, the air inside the waste liquid storage space 2840, which is sealed by the O-ring 2700, can escape to the outside. In other words, the waste liquid can flow into the storage space 2840 in the waste liquid tank 2800.
[0081] 9 shows a top view of a fluidic device 1200 having a straight channel as a comparative example, in which the solid and dashed lines are not interpreted as corresponding to whether they are visible from the top surface or not, but merely show a schematic representation of the configuration of the internal components of the fluidic device 1200.
[0082] The fluidic device 1200 has a straight (linear) space 1220 inside the main body 1210. A fluid inlet 1230 and a fluid outlet 1240 are formed near the ends of the straight space 1220. The fluid inlet 1230 and the fluid outlet 1240 are formed perpendicular to the plane of the main body 1210 or the straight space 1220. Fluid is introduced from the fluid inlet 1230 into the straight space 1220, flows within the straight space 1220 in its longitudinal direction, fills the straight space 1220, and is discharged to the outside from the fluid outlet 1240.
[0083] Sensing electrodes 1221, 1222, and 1223 are disposed in the straight space 1220, extending in the longitudinal direction thereof. In this comparative example, the sensing electrodes are three-electrode electrodes for electrochemical measurement. The sensing electrodes include a working electrode 1221, a reference electrode 1222, and a counter electrode 1223. These electrodes are connected to corresponding connection terminals 1261, 1262, and 1263 via lead wires. The connection terminals are exposed on the outer surface of the main body 1210, allowing electrical connection to be made from the outside.
[0084] <Comparison between disk type and straight type> It is generally recognized that in sensing devices that use the stop-flow method, sensing performance declines when the volume of test liquid is low. One reason for this is thought to be that, compared to a flow method in which test liquid is constantly supplied, the stop-flow method makes it difficult to completely replace the measurement space filled with test liquid with the test liquid, and it is also difficult to eliminate any trapped air bubbles. Therefore, in this experimental example, we compared the sensing performance of a disk-shaped channel and a straight channel depending on the amount of liquid introduced, particularly at low volumes. The device configuration used is as follows:
[0085] The disk-shaped flow channel had a configuration similar to that shown in Figure 7. The disk-shaped space had a diameter of 6.0 mm and a height of 0.3 mm. Therefore, the volume of the internal space was approximately 8.48 mm. 3 = 8.48 μL. Three electrodes having almost the same configuration as that shown in FIG. 7 were arranged on the bottom surface inside this space.
[0086] On the other hand, the straight flow path had an internal space of 20.5 mm in length, 3.0 mm in width, and 0.3 mm in height. Therefore, the volume of the internal space was approximately 18.45 mm. 3 = 18.45 μL. Three electrodes having almost the same configuration as that shown in FIG. 9 were arranged on the bottom surface inside this space.
[0087] On this electrode, an enzyme membrane was formed having fructosyl amino acid oxidase (FAOD) immobilized by cross-linking with bovine serum albumin (BSA).
[0088] First, a HEPES solution (10 mM HEPES, 150 mM NaCl, trace amounts of preservatives, pH 8.0) was prepared. A solution of 14-15 μM FK (fructosyl lysine) was dissolved in the HEPES solution to prepare the measurement solution. Each flow path was filled with the HEPES solution to condition the enzyme membrane for measurement. Then, multiple volumes of the measurement solution (50-1000 μL) were introduced into each flow path device using a pipette, and the time-dependent change in the current output from the electrodes was measured. In the graphs shown below, the current value measured a predetermined time (approximately 120 seconds) after the introduction of the solution was used.
[0089] Figure 10 shows the current values (vertical axis) obtained for each device versus the amount of solution (horizontal axis), where the current values are normalized with the value at 1000 μL (1 mL) set to 100%.
[0090] In the straight-type flow channel, the output dropped significantly as the volume decreased, especially below 400 μL. In other words, a decrease in output was observed at low volumes. On the other hand, in the disk-type flow channel, a decrease in output was observed below 200 μL, but even at 50 μL, the decrease in output was only about 7%. The disk-type flow channel did not exhibit the serious decrease in output at low volumes seen in the straight-type flow channel. Thus, it was found that the disk-type flow channel has high sensing performance even for low volumes of introduced solution.
[0091] The above results are considered as one possible interpretation. In a straight-type channel, the introduced test solution is thought to flow most easily through the center (the center in the width direction) of the channel due to hydrodynamics. That is, when a sufficient amount of solution (e.g., 1000 μL) is introduced, the entire volume of HEPES solution in the channel is thought to be replaced by the test solution. However, when an insufficient amount of solution is introduced (e.g., 400 μL or less), the entire volume of HEPES solution in the channel is thought to be not replaced by the test solution. Therefore, the test solution comes into contact with only a portion of the electrode's total surface area. This is thought to have led to a decrease in the measured current. This situation is thought to worsen as the amount introduced becomes smaller, which is consistent with the trend in the experimental results shown in Figure 10. In other words, the solution conversion efficiency of the straight-type channel is low, while the disk-shaped channel has a high conversion efficiency.
[0092] Furthermore, low solution conversion efficiency means that the previous solution remains. This is a phenomenon in which two different fluids come into contact, and can cause variations in solution conversion efficiency, i.e., sensing output. In fact, the inventors have observed such variations in straight flow channels. On the other hand, disk-shaped flow channels have high conversion efficiency and are less likely to cause output variations while allowing a certain amount of the previous solution to remain.
[0093] Thus, the disk-shaped flow channel has a high solution conversion efficiency for a low volume of introduced measurement solution, enabling highly sensitive and / or highly stable measurements.
[0094] The above discussion is an example, and other interpretations of the experimental results are possible. The present disclosure does not exclude other scientific and technical interpretations, considerations, theories, etc.
[0095] <Effect of the Height of the Disk-Shaped Space> In this example, the effect of the height of the disk-shaped channel on the output current characteristics was investigated. Channel devices with internal spaces of 6.0 mm diameter and 0.1 mm, 0.28 mm, 0.6 mm, and 1.0 mm heights were prepared. Three electrodes with a configuration similar to that shown in Figure 7 were placed on the bottom of the internal space.
[0096] An enzyme membrane containing fructosyl amino acid oxidase (FAOD) immobilized by cross-linking with bovine serum albumin (BSA) was formed on the electrode. The enzyme membrane had a thickness of approximately 25 μm, which was smaller than the precision of the internal space height. Thus, the four types of flow channel devices had the same bottom shape and area, the same enzyme membrane, and different internal space heights.
[0097] A HEPES solution was prepared similarly to the experiment shown in Figure 10. A substrate solution was prepared by dissolving 20 μM FK as a substrate in the HEPES solution used as a solvent. Each flow path was filled with the HEPES solution, and the enzyme membrane was prepared for measurement. Then, 100 μL of the substrate solution was introduced into each flow path device using a pipette, and the time-dependent change in the current output from the electrode was measured.
[0098] Figure 11 shows the time course of output current from the introduction of the substrate solution (time t = 0) for each flow path device. Measurements were performed on multiple flow path devices at each height; Figure 11 shows one example for each. The 0.1 mm device exhibited the highest maximum output (approximately 28 nA) and the fastest time to reach maximum output (approximately 58 seconds), but the maximum output was maintained for only a short time. The 0.28 mm device exhibited a lower maximum output (approximately 24 nA) and a slower time to reach maximum output (approximately 120 seconds), but the maximum output was maintained for a significantly longer time. The 0.6 mm and 1.0 mm devices exhibited lower maximum output and slower time to reach maximum output, but the maximum output was maintained for a longer time than the 0.28 mm device. Figure 12 shows the relationship between the height of the disk-shaped space and the maximum output maintenance time.
[0099] As shown in Figure 11, the device with a height of 0.6 mm exhibited a slightly lower maximum output current than the device with a height of 1.0 mm. However, no substantial difference was observed between the two. In other words, it is assumed that there is almost no change in the characteristics at heights of 0.6 mm or more (see Figure 12). Of course, if the height becomes extremely large, the tendency of these characteristics may change. For example, the height may be 1 mm or less. This allows the measurement volume to be kept small. Furthermore, it is possible to prevent the inclusion of air bubbles, etc.
[0100] Logically, a device with a height of 0.1 mm, which exhibits the highest maximum output current, would be expected to have the highest measurement sensitivity. However, the maximum output currents exhibited by devices with heights of 0.6 mm and 1.0 mm provide sufficient measurement sensitivity for the device disclosed herein. The time of maximum output current varies depending on the timing of introduction of substrate solution into the flow path device, the flow rate, and other factors. In other words, a longer period during which the maximum output current is maintained is advantageous for the stability of measurement results. For example, the introduction of substrate solution into the flow path device can be the starting point for calculating the measurement time. For example, the current value measured a certain time after the introduction of substrate solution into the flow path device may be used as the measurement value. Figure 12 shows the relationship between the height of the flow path device and the time during which maximum output is maintained. The time from the time when the maximum output current is applied to the time when the current value drops by 1.2 nA, the maximum value of the current data variation, is calculated as the time during which maximum output is maintained.
[0101] The 0.6 mm and 1.0 mm height devices provided a maximum output sustain time of approximately 100 seconds. In reality, the maximum output current is stable, so the error in this calculated sustain time is large. As mentioned above, in this example, although there were some differences between the 0.6 mm height device and the 1.0 mm height device, it was found that they generally exhibited the same characteristics. Therefore, as mentioned above, it is estimated that there is almost no change in the maximum output sustain time for heights of 0.6 mm or more ( FIG. 12 ).
[0102] On the other hand, the maximum output sustained time increased almost linearly and monotonically from a height of 0.1 mm to 0.6 mm ( FIG. 12 ). For example, if this time is 1 minute (60 seconds), measurements can be performed stably. A height of 0.28 mm indicates a maximum output sustained time of approximately 60 seconds, which is considered to be substantially sufficient. Therefore, in some embodiments, the height of the internal space may be 0.28 mm or more. Also, a height of 0.3 mm can provide a maximum output sustained time of approximately 60 seconds. Therefore, in some embodiments, the height of the internal space may be 0.3 mm or more. The height of the internal space may be 0.4 mm, 0.5 mm, or greater.
[0103] In this example, the enzyme membrane thickness was approximately 25 μm as described above, but the inventors have confirmed similar trends with thicknesses of 10 μm to 35 μm (not shown). When the enzyme membrane thickness was less than 10 μm, the output current value changed rapidly and its stability was low. On the other hand, when the enzyme membrane thickness was 40 μm, the diffusion of the substrate within the enzyme membrane was slow, making current measurement inefficient.
[0104] A short maximum output time often means that the current value drops sharply after the time of the maximum output current. Variations in the characteristics of the enzyme membrane occur to some extent during the manufacturing process. A configuration that causes abrupt changes in current can be a factor in reducing measurement reproducibility. Therefore, maintaining a certain period of time at which the maximum output current is maintained is meaningful, at least for the sake of high reproducibility. A long maximum output time means that the diffusion / supply rate of the substrate to the enzyme membrane, or the concentration gradient of the substrate within the enzyme membrane, remains constant for a long period of time. Therefore, high reproducibility can be achieved. Furthermore, the accuracy of the GA value measurement obtained based on the output current curve also increases.
[0105] There are various methods for calculating the GA value from the output current characteristics (also referred to as time change / curve of current, waveform data, etc.). For example, the current value at a predetermined time from the time the substrate solution is introduced into the device space may be obtained. For example, multiple current values on the current curve may be selected or obtained. For example, a statistical value may be obtained from the current curve. For example, a statistical value may be obtained from current values at multiple times. The GA value may be calculated based on one or multiple statistical values. For example, the GA value may be calculated based on the maximum output current value and the current values 10 seconds before and after that value. For example, the GA value may be calculated based on the area given by the output current curve. These are merely examples, and other calculation methods may also be used.
[0106] The present disclosure includes the following embodiments: A001 A fluidic device comprising: a device body having a disc-shaped space containing a fluid therein; a fluid inlet configured to introduce the fluid tangentially into the disc-shaped space substantially at the 0 o'clock position around the circumference of the disc-shaped space; and a fluid outlet configured to discharge the fluid from the space substantially at the 6 to 12 o'clock position around the circumference of the disc-shaped space. A011 The fluidic device of embodiment A001, wherein the fluid outlet is configured to discharge the fluid from the space substantially at the 7 to 12 o'clock position around the circumference of the disc-shaped space. A012 The fluidic device of embodiment A011, wherein the fluid outlet is configured to discharge the fluid from the space substantially at the 9 to 12 o'clock position around the circumference of the disc-shaped space. A013 The fluidic device according to any one of embodiments A001 to A012, wherein the fluid outlet is arranged in the disk-shaped space at a position counterclockwise from the inlet (upstream in the direction of fluid flow). A021 The fluidic device according to any one of embodiments A001 to A013, wherein the volume of the disk-shaped space is 1 μL to 100 μL. A022 The fluidic device according to embodiment A021, wherein the volume of the disk-shaped space is 3 to 20 μL. A023 The fluidic device according to embodiment A021, wherein the height of the disk-shaped space is any one of or greater than 0.28 mm, 0.3 mm, 0.4 mm, 0.5 mm, and 0.6 mm. A025 The fluidic device according to any one of embodiments A001 to A023, wherein the sum of the volume of the disk-shaped space and the volume of the fluid inlet is 2 μL to 200 μL. A026 The fluidic device according to embodiment A025, wherein the sum of the volume of the disk-shaped space and the volume of the fluid inlet is 6 μL to 40 μL.A027 The fluidic device according to any one of embodiments A001 to A026, wherein the volume of the fluid inlet is substantially 50%, 100%, 150%, or 200% of the volume of the disk-shaped space. A031 The fluidic device according to any one of embodiments A001 to A027, further comprising a sensor on the inner wall of the disk-shaped space. A032 The fluidic device according to embodiment A031, wherein the sensor is a biosensor. A033 The fluidic device according to embodiment A031 or A032, wherein the sensor has an electrode. A034 The fluidic device according to embodiment A033, wherein the electrode has a hydrogen peroxide electrode. A035 The fluidic device according to embodiment A034, wherein the sensor further comprises an enzyme membrane on the hydrogen peroxide electrode. A036 The fluidic device according to embodiment A035, wherein the enzyme membrane comprises an oxidase. A037 The fluidic device according to embodiment A036, wherein the oxidase is a FAOD. A038 The fluidic device according to any one of embodiments A035 to A037, wherein the enzyme membrane comprises a protease. A039 The fluidic device according to embodiment A036, wherein the oxidase is glucose oxidase. A041 The fluidic device according to any one of embodiments A031 to A039, wherein the sensor is a protein sensor. A042 The fluidic device according to embodiment A041, wherein the sensor comprises a glycoalbumin sensor and / or an albumin sensor. A051 The fluidic device of any one of embodiments A031 to A042, comprising or configured to be combined with an optical sensor outside the disc-shaped space. A061 The fluidic device of any one of embodiments A001 to A051, which is a stop-flow fluidic device.
[0107] Several embodiments and examples of the present disclosure have been described above, but these embodiments and examples exemplify the present disclosure. For example, the above embodiments have been described in detail to clearly explain the present disclosure, and additional changes in dimensions, configurations, materials, and circuits may be made as necessary. Note that embodiments that combine any one or more features of the present disclosure described above are also included within the scope of the present disclosure. The claims encompass numerous modifications to the embodiments without departing from the technical spirit of the present disclosure. Therefore, the embodiments and examples disclosed herein are provided for illustrative purposes and should not be considered to limit the scope of the present disclosure.
Claims
1. A device body having a disk-shaped space inside for containing fluid; A fluid inlet configured to introduce the fluid tangentially at the 0 o'clock position on the substantially circumferential portion of the disk-shaped space; and A fluid outlet configured to discharge the fluid from the disk-shaped space at a position from 6 o'clock to 12 o'clock on the substantially circumferential portion of the disk-shaped space; A fluid device equipped with the following features.
2. A fluid device according to claim 1, The fluid outlet is configured to guide the fluid out of the space at a position from 7 o'clock to 12 o'clock on the substantially circumferential part of the disk-shaped space. Fluid devices.
3. A fluid device according to claim 2, The fluid outlet is configured to guide the fluid out of the space at the 9 o'clock to 12 o'clock position on the substantially circumferential part of the disk-shaped space. Fluid devices.
4. A fluid device according to claim 1, The fluid outlet is located in the disk-shaped space, counterclockwise from the inlet. Fluid devices.
5. A fluid device according to claim 1, The volume of the disk-shaped space is 1 μL to 100 μL. Fluid devices.
6. A fluid device according to claim 5, The height of the aforementioned disc-shaped space is 0.3 mm or more. Fluid devices.
7. A fluid device according to claim 1, The sum of the volume of the disk-shaped space and the volume of the fluid inlet is between 2 μL and 200 μL. Fluid devices.
8. A fluid device according to claim 1, The volume of the fluid inlet is substantially 50%, 100%, 150%, or 200% of the volume of the disk-shaped space. Fluid devices.
9. A fluid device according to claim 1, A sensor is located on the inner wall of the aforementioned disc-shaped space. A fluid device further equipped with [the following features].
10. A fluid device according to claim 9, The aforementioned sensor is a biosensor. Fluid devices.
11. A fluid device according to claim 10, The sensor has an electrode, and the electrode has a hydrogen peroxide electrode. Fluid devices.
12. A fluid device according to claim 11, The sensor further comprises an enzyme membrane on the hydrogen peroxide electrode. Fluid devices.
13. A fluid device according to claim 12, The enzyme membrane contains FAOD and protease. Fluid devices.
14. A fluid device according to claim 12 or 13, The enzyme membrane contains glucose oxidase. Fluid devices.
15. A fluid device according to claim 10, The sensor comprises a glycoalbumin sensor and / or an albumin sensor. Fluid devices.
16. A fluid device according to claim 1, A fluid device comprising an optical sensor outside a disk-shaped space, or configured to be combined with an optical sensor outside a disk-shaped space.
17. A fluid device according to claim 1, A fluid device that is a stop-flow fluid device.